levodopa

Research Excerpts

Overview

Levodopa (L-DOPA) is an essential drug for the treatment of Parkinson's disease. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion.

Excerpt	Reference	Relevance
"Levodopa is a precursor of dopamine, having important beneficial effects in the treatment of Parkinson's disease. "	( Voltammetric Determination of Levodopa Using Mesoporous Carbon-Modified Screen-Printed Carbon Sensors. Apetrei, C; Dăscălescu, D, 2021)	2.35
"Levodopa (L-DOPA) is an oral Parkinson's Disease drug that generates the active metabolite - dopamine (DA) in vivo. "	( Particulate levodopa nose-to-brain delivery targets dopamine to the brain with no plasma exposure. Akcan, O; Dimiou, S; Huang, H; Kubajewska, I; Lopes, RM; Mellor, RD; Schätzlein, AG; Schlosser, CS; Shet, MS; Uchegbu, IF; Whiteside, GT, 2022)	2.54
"Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease."	( Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Aldred, J; Budur, K; Facheris, MF; Fisseha, N; Fung, VS; Hauser, RA; Jeong, A; Kimber, TE; Klos, K; Litvan, I; O'Neill, D; Robieson, WZ; Soileau, MJ; Spindler, MA; Standaert, DG; Talapala, S; Vaou, EO; Zheng, H, 2022)	1.49
"Levodopa (L-DOPA) is an essential drug for the treatment of Parkinson's disease. "	( Enhanced Physicochemical Stability of the L-DOPA Extract of Kobtrakul, K; Vilairat, C; Vimolmangkang, S, 2023)	2.35
"Levodopa is a precursor to dopamine that has been shown to improve functional recovery following stroke partly achieved through mechanisms of brain plasticity. "	( Enhanced functional recovery by levodopa is associated with decreased levels of synaptogyrin following stroke in aged mice. Häggman Henrikson, J; Pombo Antunes, AR; Ruscher, K; Wieloch, T, 2020)	2.28
"Levodopa (L-dopa) is an effective medication for alleviating motor symptoms in PD that has been shown previously to reduce subcortical beta (13-30 Hz) oscillations."	( L-dopa treatment increases oscillatory power in the motor cortex of Parkinson's disease patients. Cao, C; Li, D; Litvak, V; Sun, B; Zhan, S; Zhang, C, 2020)	1.28
"Levodopa or l-Dopa is an amino acid used in the treatment of PD that acts as the immediate precursor to dopamine."	( L-Dopa release from mesoporous silica nanoparticles engineered through the concept of drug-structure-directing agents for Parkinson's disease. Almendro, N; García-Muñoz, RA; McConnell, J; Morales, V; Pérez-Garnes, M; Sanz, R, 2021)	1.34
"Levodopa is a drug that is commonly used to treat movement disorders associated with Parkinson's disease. "	( Using epigenetic networks for the analysis of movement associated with levodopa therapy for Parkinson's disease. Alty, JE; Cosgrove, J; Jamieson, S; Lones, MA; Smith, SL; Trefzer, MA; Turner, AP; Tyrrell, AM, 2016)	2.11
"Levodopa (L-dopa) is a "gold standard" and most effective symptomatic agent in the Parkinson's disease (PD) treatment. "	( Protective effect of two essential oils isolated from Rosa damascena Mill. and Lavandula angustifolia Mill, and two classic antioxidants against L-dopa oxidative toxicity induced in healthy mice. Gadjeva, V; Karamalakova, Y; Kovacheva, N; Nikolova, G; Stanev, S; Zheleva, A, 2016)	1.88
"Levodopa is a promising candidate for administration via the transdermal route because it exhibits a short plasma half-life and has a small window of absorption in the upper section of the small intestine. "	( Enhancement of levodopa stability when complexed with β-cyclodextrin in transdermal patches. Al-Shar'i, N; Athamneh, T; Obaidat, R; Tashtoush, B, 2018)	2.28
"Levodopa is a potent alternative and can be given if there is an inadequate response to the agonist."	( [Initial management and adaptation of Parkinson's disease treatment]. Gérard, JM, 2008)	1.07
"Levodopa (LD) is an efficient drug for patients with Parkinson's disease (PD). "	( Entacapone. Müller, T, 2010)	1.8
"Etilevodopa is a unique, highly soluble prodrug of levodopa."	( Pharmacokinetics of etilevodopa compared to levodopa in patients with Parkinson's disease: an open-label, randomized, crossover study. Djaldetti, R; Giladi, N; Hassin-Baer, S; Melamed, E; Shabtai, H, )	0.96
"Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration."	( A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations. Blindauer, K; Eyal, E; Fahn, S; Goetz, C; Goren, S; Kieburtz, K; Levy, R; Nutt, J; Oakes, D; Pagano, M; Salzman, P; Sayag, N; Schwid, S; Scolnik, M; Shoulson, I; Stern, M, 2006)	1.12
"Levodopa is a dopamine precursor exerting its cardiovascular effects by conversion to dopamine and by other mechanisms not elucidated yet. "	( The beta 2 receptor plays a role in the hypotensive effect of L-dopa. Pérez-Olea, J; Prieto, JC; Quevedo, M, 1995)	1.73
"Levodopa is a useful adjunctive therapy in HIV-1-infected children with extrapyramidal syndromes, by enhancing motor function and improving their quality of life."	( Levodopa therapy improves motor function in HIV-infected children with extrapyramidal syndromes. Hoyt, L; McSherry, G; Mendelson, J; Mintz, M; Oleske, J; Tardieu, M, 1996)	2.46

Effects

Melevodopa/carbidopa has a more rapid absorption, less apparent drug accumulation, less inter-patient variability and more effective LD delivery after the early morning and early afternoon dose compared to standard LD. Levodopa itself has a very poor solubility.

Levodopa has become the main therapy for motor symptoms of Parkinson's disease (PD) The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. Foslevodopa-foscarbidopa has a favourable benefit-risk profile.

Excerpt	Reference	Relevance
"Foslevodopa-foscarbidopa has a favourable benefit-risk profile and represents a potential non-surgical alternative for patients with advanced Parkinson's disease."	( Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Aldred, J; Budur, K; Facheris, MF; Fisseha, N; Fung, VS; Hauser, RA; Jeong, A; Kimber, TE; Klos, K; Litvan, I; O'Neill, D; Robieson, WZ; Soileau, MJ; Spindler, MA; Standaert, DG; Talapala, S; Vaou, EO; Zheng, H, 2022)	1.49
"Melevodopa/carbidopa has a more rapid absorption, less apparent drug accumulation, less inter-patient variability and more effective LD delivery after the early morning and early afternoon dose compared to standard LD. "	( A systematic review on the clinical experience with melevodopa/carbidopa fixed combination in patients with Parkinson disease. Stocchi, F; Vacca, L, 2019)	1.48
"Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease."	( Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. Dhall, R; Kreitzman, DL, 2016)	1.53
"Levodopa has an established position in the treatment of Parkinson's disease for the last 40 years. "	( [Levodopa in the treatment of Parkinson disease -- yesterday and today]. Sławek, J, )	2.48
"Levodopa has a central role in the metabolism of the melanocyte but data do not permit the conclusion that it promotes the development of malignant melanoma."	( Malignant melanoma and levodopa. Braun, M; Rosin, MA, 1984)	1.3
"Levodopa itself has a very poor solubility."	( Current management of motor fluctuations in patients with advanced Parkinson's disease treated chronically with levodopa. Djaldetti, R; Galili-Mosberg, R; Melamed, E; Ziv, I; Zoldan, J, 1999)	1.24
"Levodopa has become the main therapy for motor symptoms of Parkinson's disease (PD). "	( The amplitude of low-frequency fluctuation predicts levodopa treatment response in patients with Parkinson's disease. Bai, Y; Gao, D; Guo, Z; Hu, W; Li, Z; Liu, C; Mo, J; Wang, X; Wang, Y; Yang, B; Zhang, C; Zhang, J; Zhang, K; Zhang, X; Zhao, B; Zhao, X; Zou, L, 2021)	2.31
"The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. "	( L-DOPA coating improved phosphate glass fibre strength and fibre/matrix interface. Ahmed, I; Parsons, AJ; Rudd, CD; Sharmin, N; Tan, C, 2022)	1.28
"Foslevodopa-foscarbidopa has a favourable benefit-risk profile and represents a potential non-surgical alternative for patients with advanced Parkinson's disease."	( Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Aldred, J; Budur, K; Facheris, MF; Fisseha, N; Fung, VS; Hauser, RA; Jeong, A; Kimber, TE; Klos, K; Litvan, I; O'Neill, D; Robieson, WZ; Soileau, MJ; Spindler, MA; Standaert, DG; Talapala, S; Vaou, EO; Zheng, H, 2022)	1.49
"Melevodopa/carbidopa has a more rapid absorption, less apparent drug accumulation, less inter-patient variability and more effective LD delivery after the early morning and early afternoon dose compared to standard LD. "	( A systematic review on the clinical experience with melevodopa/carbidopa fixed combination in patients with Parkinson disease. Stocchi, F; Vacca, L, 2019)	1.48
"Levodopa has been a standard drug for treating Parkinson's disease since the 1960s, but it has caused many side effects such as wearing-off, motor fluctuation, and dystonia. "	( Glutathione-decorated fluorescent carbon quantum dots for sensitive and selective detection of levodopa. Jung, YK; Kim, TE; Park, SW, 2021)	2.28
"Levodopa has been shown to impair reward-based learning in cognitive tasks."	( Null effects of levodopa on reward- and error-based motor adaptation, savings, and anterograde interference. Gribble, PL; MacDonald, PA; McGregor, HR; Palidis, DJ; Vo, A, 2021)	1.69
"Levodopa has the best safety data for use in pregnancy and amantadine should be avoided in women who are pregnant or trying to become pregnant."	( Parkinson's disease and pregnancy: An updated review. Hiller, A; Seier, M, 2017)	1.18
"Levodopa has been the mainstay of symptomatic therapy for Parkinson's disease (PD) for the last five decades. "	( Modulatory Effects of Levodopa on Cerebellar Connectivity in Parkinson's Disease. Ballarini, T; Holiga, Š; Jech, R; Möller, HE; Mueller, K; Piecha, FA; Růžička, E; Růžička, F; Schroeter, ML; Vymazal, J, 2019)	2.27
"Levodopa has decreasing efficacy over time."	( The association between Parkinson's disease symptom side-of-onset and performance on the MDS-UPDRS scale part IV: Motor complications. Bay, AA; Corcos, DM; Hackney, ME; Hart, AR; Michael Caudle, W, 2019)	1.24
"Levodopa has long been the standard of care for Parkinson disease (PD); however, the eventual onset of motor fluctuations and levodopa-induced dyskinesia (LID) complicates its utility in advanced PD. "	( Neurosurgical Approaches to Levodopa-Induced Dyskinesia. Martini, ML; Mocco, J; Panov, F, 2019)	2.25
"Oral levodopa has been proposed to be one of the more effective medications to alleviate freezing of gait, but there is limited data on its efficacy. "	( Levodopa changes the severity of freezing in Parkinson's disease. Ceballos-Baumann, AO; Fietzek, UM; Schroeteler, FE; Ziegler, K; Zwosta, J, 2013)	2.35
"Oral levodopa has been widely used for over 40 years, often in combination with a dopa-decarboxylase inhibitor (DDCI), which reduces many treatment complications, extending its half-life and increasing levodopa availability to the brain."	( Levodopa in the treatment of Parkinson's disease: current status and new developments. Salat, D; Tolosa, E, 2013)	2.29
"Levodopa has been demonstrated to be an effective medication for Parkinson's disease (PD), but its long-term use is complicated by the subsequent development of dyskinesias. "	( The relationship between the phenotype of Parkinson's disease and levodopa-induced dyskinesia. Guo, JF; Liu, ZH; Lou, MX; Song, CY; Tang, BS; Xu, Q; Yan, XX; Yu, RH; Zhang, YH, 2013)	2.07
"Levodopa (L-dopa) has been at the forefront of antiparkinsonian therapy for a half century. "	( Effects of levodopa on regional cerebral metabolism and blood flow. Eidelberg, D; Ko, JH; Lerner, RP, 2015)	2.25
"Levodopa treatment has been shown to improve gait spatio-temporal characteristics in both forward and backward walking. "	( Gait variability in Parkinson's disease: levodopa and walking direction. Bryant, MS; Collins, RL; Hou, JG; Protas, EJ; Rintala, DH, 2016)	2.14
"Levodopa has remained the "gold standard" of the therapy even several decades after its introduction."	( [Application of levodopa/carbidopa intestinal gel in advanced Parkinson's disease]. Bereczki, D; Nagy, H; Takáts, A; Toth, A; Wacha, J, 2015)	1.48
"Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease."	( Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. Dhall, R; Kreitzman, DL, 2016)	1.53
"Levodopa therapy has no unfavorable effect on left ventricular systolic function in patients with PD."	( Effects of levodopa therapy on global left ventricular systolic function in patients with Parkinson disease. Bektaş, O; Günaydın, ZY; Karagöz, A; Özer, FF, 2016)	2.27
"Levodopa (l-DOPA) has been proved to reverse the pathologic neuron activities in many brain regions related to Parkinson's disease (PD). "	( Effect of l-DOPA on local field potential relationship between the pedunculopontine nucleus and primary motor cortex in a rat model of Parkinson's disease. Geng, X; Han, H; Hou, Y; Lei, C; Li, M; Wang, M; Wang, X; Xie, J; Yao, X; Zhang, Q; Zhang, X, 2016)	1.88
"Levodopa has been the mainstay of symptomatic therapy for Parkinson Disease (PD) for 40 years providing benefit to virtually all patients. "	( Levodopa unresponsive symptoms in Parkinson disease. Sethi, K, 2008)	3.23
"Levodopa has been the mainstay of treatment for Parkinson's disease (PD) for more than 40 years. "	( Levodopa: past, present, and future. Hauser, RA, 2009)	3.24
"As levodopa abuse has only been described in patients with PD, it was suspected to be promoted by central dopamine depletion (with consequent sensitization of dopamine receptors)."	( Dopamine dysregulation syndrome in a patient with restless legs syndrome. Arnulf, I; Brion, A; Karroum, E; Konofal, E; Leu-Semenescu, S, 2009)	0.87
"Levodopa has been the gold standard therapy for the motor symptoms of Parkinson's disease for more than three decades. "	( Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Truong, DD, 2009)	1.8
"Levodopa has been used successfully for treatment of PD since its discovery, being still the drug of choice. "	( [Reconsiderations in the treatment of Parkinson's disease with levodopa: some pharmacodynamic evidence]. Muñoz-S, D; Nicoletti, A; Tapia-Núñez, J; Zappia, M, )	1.81
"Levodopa has been shown to produce analgesia in various clinical and experimental settings, but its use for chronic pain treatment has not been established. "	( Levodopa analgesia in experimental neuropathic pain. Cobacho, N; De la Calle, JL; González-Escalada, JR; Paíno, CL, 2010)	3.25
"Levodopa/carbidopa CR has previously been found effective for treating night-time akinesia, but according to this study, it has no impact on the altered sleep structure in PD."	( Effect of controlled-release levodopa on the microstructure of sleep in Parkinson's disease. Deuschl, G; Herzog, J; Volkmann, J; Wailke, S; Witt, K, 2011)	2.1
"Levodopa has been the mainstay of treatment for Parkinson's disease since the 1960s, but the dyskinesias it induces are a major drawback. "	( [Stimulation therapies for Parkinson's disease: over the past two decades]. Benabid, AL, 2010)	1.8
"Levodopa has been the mainstay of Parkinson's disease (PD) therapy for over 40 years, with its efficacy surpassing that of other antiparkinsonian medications. "	( Optimizing levodopa therapy to treat wearing-off symptoms in Parkinson's disease: focus on levodopa/carbidopa/entacapone. Emre, M; Reichmann, H, 2012)	2.21
"Levodopa has an established position in the treatment of Parkinson's disease for the last 40 years. "	( [Levodopa in the treatment of Parkinson disease -- yesterday and today]. Sławek, J, )	2.48
"Levodopa has several advantages as a pharmacological challenge agent for human neuroscience research. "	( Rapid intravenous loading of levodopa for human research: clinical results. Black, KJ; Carl, JL; Hartlein, JM; Hershey, T; Perlmutter, JS; Warren, SL, 2003)	2.05
"Levodopa therapy has numerous advantages that include greater efficacy, much lesser expense, simpler administration, and a lower frequency of hallucinosis and somnolence."	( Parkinson's disease: is the initial treatment established? Ahlskog, JE, 2003)	1.04
"Levodopa treatment has been shown to increase plasma homocysteine levels in Parkinson's disease (PD) patients and this may lead to an increased risk for coronary arterial diseases. "	( The COMT inhibitor, entacapone, reduces levodopa-induced elevations in plasma homocysteine in healthy adult rats. Helkamaa, T; Larjonmaa, H; Nissinen, E; Nissinen, H; Rauhala, P; Reenilä, I; Väänänen, A, 2005)	2.04
"Levodopa has been the gold standard for Parkinson's disease (PD) therapy since it was successfully introduced in 1967. "	( A new look at levodopa based on the ELLDOPA study. Fahn, S, 2006)	2.14
"Levodopa has been incriminated in the development and/or progression of melanoma."	( [CDKN2A gene mutation and loss of p16 protein activity in a patient on levodopa presenting sporadic multiple primary melanoma]. Bressac de Paillerets, B; Charles, J; Combe, MC; Leccia, MT; Leroux, D; Templier, I, 2006)	1.29
"Levodopa has been the mainstay treatment for Parkinson's disease for several decades, but the precise mechanism for its therapeutic action is still not well understood. "	( Different levodopa actions on the extracellular dopamine pools in the rat striatum. Dopico, JG; Gómez, I; González-Mora, JL; Morales, I; Obeso, JA; Rodríguez, M; Rodríguez-Oroz, MC; Sabaté, M, 2007)	2.18
"Levodopa has played a central role in the treatment of Parkinson's disease for nearly 40 years and remains the single most effective symptomatic treatment for the disease. "	( Balancing short-term symptom control and long-term functional outcomes in patients with Parkinson's disease. Tetrud, JW, 2007)	1.78
"Levodopa has also consistently been shown to produce motor fluctuations (in particular dyskinesias) sooner than has been observed in PD patients, especially younger patients, given dopamine agonists initially."	( When should levodopa therapy be initiated in patients with Parkinson's disease? Fernandez, HH; Halkias, IA; Haq, I; Huang, Z, 2007)	1.44
"Levodopa has a central role in the metabolism of the melanocyte but data do not permit the conclusion that it promotes the development of malignant melanoma."	( Malignant melanoma and levodopa. Braun, M; Rosin, MA, 1984)	1.3
"Levodopa has been implicated as an agent that could enhance the development of MM."	( Malignant melanoma and levodopa: is there a relationship? Two new cases and a review of the literature. Pfützner, W; Przybilla, B, 1997)	1.33
"Levodopa has been used to treat some painful conditions and found to be effective in neuropathic pain due to herpes zoster in a double-blind study. "	( Use of levodopa to relieve pain from painful symmetrical diabetic polyneuropathy. Arac, N; Ertas, M; Ertekin, C; Sagduyu, A; Uludag, B, 1998)	2.2
"Levodopa itself has a very poor solubility."	( Current management of motor fluctuations in patients with advanced Parkinson's disease treated chronically with levodopa. Djaldetti, R; Galili-Mosberg, R; Melamed, E; Ziv, I; Zoldan, J, 1999)	1.24
"Both levodopa and biperiden has less effect on postural tremor."	( A cross-over clinical and electromyographic assessment of treatment for parkinsonian tremor. Milanov, I, 2001)	0.77
"Levodopa has been shown to be a safe pharmacologic agent even after long-term usage."	( Levodopa. Yahr, MD, 1975)	2.42
"Levodopa clearly has no place in the treatment of neuroleptic-induced Parkinson's disease; anticholinergics and antihistamines are the agents of choice."	( Pharmacotherapy of Parkinson's disease. Cohen, MM; Scheife, RT, 1977)	0.98
"Levodopa has become established as the treatment of choice in Parkinson's disease. "	( A review of some aspects of the pharmacology of levodopa. Morris, JG, 1978)	1.96
"Levodopa has been demonstrated to exert both central and peripheral effects on blood pressure in parkinsonian patients."	( Central and peripheral catecholamine mechanisms in circulatory control. Dollery, CT; Reid, JL, 1976)	0.98
"Levodopa-carbidopa has been widely used in the treatment of Parkinson's disease. "	( Inhibition of transformation by levodopa-carbidopa in lymphocytes derived from patients with melanoma. Wick, MM, 1987)	2

Actions

Levodopa can increase CBF by dilating proximal arteries. On levodopa, there was an increase in PPNa alpha (5-12 Hz) oscillatory activity and a decrease in beta (13-35 Hz) and gamma (65-90 Hz) bands activity.

Excerpt	Reference	Relevance
"Levodopa can increase CBF by dilating proximal arteries."	( Effects of Levodopa Therapy on Cerebral Arteries and Perfusion in Parkinson's Disease Patients. Chen, L; Chen, Z; Guo, H; He, L; Ji, L; Li, X; Ma, Y; Shirakawa, M; Xiong, Y; Yuan, C; Zhang, X; Zhao, H, 2022)	2.55
"ON levodopa, there was an increase in PPNa alpha (5-12 Hz) oscillatory activity and a decrease in beta (13-35 Hz) and gamma (65-90 Hz) bands activity."	( Pedunculopontine nucleus area oscillations during stance, stepping and freezing in Parkinson's disease. Bastin, J; Benabid, AL; Chabardes, S; David, O; Debû, B; Ferraye, M; Fraix, V; Goetz, L; Pollak, P, 2013)	0.9
"Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically."	( The network of causal interactions for beta oscillations in the pedunculopontine nucleus, primary motor cortex, and subthalamic nucleus of walking parkinsonian rats. Chang, J; Li, M; Li, X; Luo, F; Wang, J; Wang, N; Wang, Q; Wen, P; Xiao, H; Xie, Z; Yang, Y; Zhang, W; Zhou, M, 2016)	1.16
"Levodopa appears to increase DA output by activating these nonfiring neurons; as a consequence, DA release is increased, but behavioral demand can now overwhelm the system, potentially leading to the inactivation and on/off phenomena."	( Physiology of the normal and dopamine-depleted basal ganglia: insights into levodopa pharmacotherapy. Grace, AA, 2008)	1.3
"Levodopa led to an increase in mtDNA levels."	( Mitochondrial abnormalities in the putamen in Parkinson's disease dyskinesia. Kaczmarska, J; Konradi, C; Luksik, AS; Naydenov, AV; Vassoler, F, 2010)	1.08
"This levodopa-induced increase in striatal quinoprotein was almost completely suppressed by adjunctive administration with pergolide on the lesioned side."	( Dopamine agonist pergolide prevents levodopa-induced quinoprotein formation in parkinsonian striatum and shows quenching effects on dopamine-semiquinone generated in vitro. Asanuma, M; Diaz-Corrales, FJ; Miyazaki, I; Miyoshi, K; Ogawa, N, )	0.86
"Levodopa induces lower cortisol plasma levels and decreases serotonergic activity in certain brain areas of fish."	( Acute levodopa intake and associated cortisol decrease in patients with Parkinson disease. Muhlack, S; Müller, T, )	1.33
"Levodopa caused an increase in plasma growth hormone concentration in 30 subjects."	( Plasma DOPA levels and growth hormone response to levodopa in parkinsomism. Galea-Debono, A; Jenner, P; Marsden, CD; Parkes, JD; Tarsy, D; Walters, J, 1977)	1.23
"Levodopa induced an increase of about 400 fold in urinary DA; DOPAC was increased about 300 fold, 3-MT only about 70 fold, but HVA about 300 fold."	( Urinary excretion of monoamines and their metabolites in patients with Parkinson's disease. Response to long-term treatment with levodopa alone or in combination with a dopa decarboxylase inhibitor and clinical correlations. Rinne, UK; Siirtola, T; Sonninen, V, 1975)	1.18
"Levodopa given alone increase the expression of c-fos mRNA."	( Muscarinic cholinergic receptor-mediated modulation on striatal c-fos mRNA expression induced by levodopa in rat brain. Asanuma, M; Chou, H; Hirata, H; Mori, A; Ogawa, N, 1992)	1.22
"Levodopa did not produce any positive inotropic effect at concentrations up to 3 X 10(-3) M."	( The inotropic effects of dopamine and its precursor levodopa on isolated human ventricular myocardium. Brown, L; Erdmann, E; Lorenz, B, 1985)	1.24

Treatment

Levodopa treatment is used to reduce rigidity and bradykinesia in Parkinson's disease. Levodopa/DDI long-term treatment contributes to altered levels of substrates of the O-methylation cycle in PP.

Excerpt	Reference	Relevance
"Levodopa treatment remains the gold standard for Parkinson's disease, but shortcomings related to the pharmacological profile, notably, oral administration and the consequent occurrence of motor complications, have led to the development of several add-on levodopa treatments or to research to improve the method of delivery. "	( COMT Inhibitors in the Management of Parkinson's Disease. Fabbri, M; Ferreira, JJ; Rascol, O, 2022)	2.16
"Levodopa treatment was associated with greater slowing of progression in the tremor domain than the nontremor domain regardless of inosine exposure."	( Dissecting the Domains of Parkinson's Disease: Insights from Longitudinal Item Response Theory Modeling. Chan, J; Goetz, CG; Luo, S; Macklin, EA; Oakes, D; Schwarzschild, MA; Simuni, T; Stebbins, GT; Zou, H, 2022)	1.44
"Levodopa treatment of Parkinson's disease tends to further elevate circulating homocysteine levels due to the metabolism of levodopa via catechol-O-methyltransferase (COMT)."	( Levodopa, homocysteine and Parkinson's disease: What's the problem? Ahlskog, JE, 2023)	3.07
"Levodopa treatment remains the most common treatment, especially for older patients."	( Treatment Patterns in Patients with Incident Parkinson's Disease in the United States. Boess, F; Constantinovici, N; Ding, Y; Freitas, R; Houghton, R; Ong, R; Verselis, L, 2019)	1.24
"Levodopa treatment could induce protective cardiac effects through the increased Hsp27 activity. "	( Cardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys. Almela, P; Bautista-Hernández, V; Cuenca-Bermejo, L; de Pablos, V; Estrada, C; Fernández-Villalba, E; Herrero, MT; Laorden, ML; Yuste, JE, 2020)	2
"Levodopa (L-DOPA) treatment in Parkinson's disease is limited by the emergence of L-DOPA-induced dyskinesia. "	( The Multimodal Serotonergic Agent Vilazodone Inhibits L-DOPA-Induced Gene Regulation in Striatal Projection Neurons and Associated Dyskinesia in an Animal Model of Parkinson's Disease. Altwal, F; Moon, C; Steiner, H; West, AR, 2020)	2
"Levodopa-treated PD patients had higher plasma Hcy than levodopa-naive PD patients. "	( Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson's disease patients: A randomized controlled study. Anamnart, C; Kitjarak, R, 2021)	2.3
"Levodopa is the main treatment for symptoms of Parkinson's disease. "	( Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease. Bloem, BR; Boel, JA; de Bie, RMA; de Haan, RJ; Deuschl, G; Dijkgraaf, MGW; Lang, AE; Munts, AG; Post, B; Suwijn, SR; Tissingh, G; van Hilten, JJ; van Laar, T; Verschuur, CVM, 2019)	2.24
"Levodopa treatment does improve Parkinson's disease (PD) dysgraphia, but previous research is not in agreement about which aspects are most responsive. "	( Effect of levodopa on handwriting tasks of different complexity in Parkinson's disease: a kinematic study. Arjunan, SP; Kempster, P; Kumar, D; Nagao, KJ; Raghav, S; Viswanthan, R; Wong, K; Zham, P, 2019)	2.36
"Levodopa treatment trial was initiated without a response."	( Bupropion Causes Misdiagnosis in Brain Dopamine Transporter Imaging for Parkinsonism. Honkanen, EA; Joutsa, J; Kaasinen, V; Kemppainen, N; Noponen, T; Seppänen, M, )	0.85
"Levodopa and placebo treated animals exhibited a similar number of surviving dopaminergic cells in the SN."	( Levodopa induces long-lasting modification in the functional activity of the nigrostriatal pathway. Arbizu, J; Collantes, M; DiCaudo, C; Luquin, MR; Marcilla, I; Ordóñez, C; Peñuelas, I; Riverol, M, 2014)	2.57
"Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT."	( Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study. Barbui, C; Bovi, T; Cannas, A; Ceravolo, R; Cipriani, A; Dallocchio, C; Di Stefano, A; Frosini, D; Luca, A; Marrosu, F; Matinella, A; Minafra, B; Morgante, F; Morgante, L; Nicoletti, A; Pacchetti, C; Rossi, S; Sciarretta, M; Solla, P; Tinazzi, M; Ulivelli, M; Zappia, M, 2014)	1.34
"Levodopa treatment is the major pharmacotherapy for Parkinson's disease. "	( Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia. Cenci, MA; Fenster, RJ; Francardo, V; Greengard, P; Heilbut, A; Heiman, M; Kolaczyk, ED; Kulicke, R; Mesirov, JP; Surmeier, DJ, 2014)	2.08
"Levodopa treatment reduced low-frequency activity and increased high-frequency activity in all three areas, but did not affect coherence."	( Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys. Bliwise, D; Devergnas, A; Pittard, D; Wichmann, T, 2014)	1.12
"Levodopa is first line treatment of Parkinson's disease (PD). "	( Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in Parkinson's disease patients? Altmann, V; Callegari-Jacques, SM; Hutz, MH; Rieck, M; Rieder, CR; Schneider Medeiros, M; Schumacher-Schuh, AF, 2015)	2.12
"Levodopa treatment increased the specific binding of NMDA receptors in the basal ganglia."	( Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy. Di Paolo, T; Grégoire, L; Jourdain, VA; Morin, N; Morissette, M, 2015)	1.14
"Levodopa treatment in Parkinson's disease (PD) causes motor fluctuations and dyskinesias, but few data describe their development or severity in unselected incident cohorts."	( Motor complications in an incident Parkinson's disease cohort. Counsell, CE; Macleod, AD; Scott, NW, 2016)	1.88
"Levodopa treatment has been shown to improve gait spatio-temporal characteristics in both forward and backward walking. "	( Gait variability in Parkinson's disease: levodopa and walking direction. Bryant, MS; Collins, RL; Hou, JG; Protas, EJ; Rintala, DH, 2016)	2.14
"No levodopa-treated participant had any adverse event from the levodopa."	( Levodopa as a possible treatment of visual loss in nonarteritic anterior ischemic optic neuropathy. Johnson, LN; Lyttle, DP; Madsen, RW; Margolin, EA, 2016)	2.39
"Levodopa is the main treatment method for reducing the symptoms of Parkinson's disease. "	( Autonomic nervous system response to L-dopa in patients with advanced Parkinson's disease. Karjalainen, PA; Pekkonen, E; Rissanen, SM; Ruonala, V; Tarvainen, MP, 2015)	1.86
"Levodopa treatment was effective in 13 out of 24 treated patients (54.16%) and in 3 patients unilateral thalamotomy provided excellent results."	( Holmes tremor: Clinical description, lesion localization, and treatment in a series of 29 cases. Calandra, C; Calvo, DS; Cersosimo, MG; Fernandez Pardal, MM; Folgar, SS; Giannaula, RJ; Giugni, JC; Micheli, FE; Paviolo, JP; Pellene, LA; Raina, GB; Tkachuk, VA; Tschopp, AL; Uribe Roca, MC; Velez, M; Zuñiga Ramirez, C, 2016)	1.16
"Levodopa treatment should be considered because it might be beneficial in some patients."	( Persistent pain as a non-motor symptom in corticobasal syndrome. Iwata, A; Ohtomo, R; Tsuji, S, 2016)	1.16
"Levodopa is first-line treatment of Parkinson's disease motor symptoms but, dose response is highly variable. "	( Influence of genetic, biological and pharmacological factors on levodopa dose in Parkinson's disease. Altmann, V; Callegari-Jacques, SM; Hutz, MH; Rieck, M; Rieder, CR; Schumacher-Schuh, AF, 2016)	2.12
"Levodopa (L-dopa) treatment of Parkinson's disease (PD) is associated with elevated homocysteine (Hcy). "	( Homocysteine is not associated with global motor or cognitive measures in nondemented older Parkinson's disease patients. Bouchard, TP; Camicioli, RM; Somerville, MJ, 2009)	1.8
"Levodopa treatment and subthalamic nucleus (STN) stimulation improve step length and walking speed, with less effect on postural instability."	( Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease. Agid, Y; Bardinet, E; Chastan, N; Do, MC; Welter, ML; Westby, GW; Yelnik, J, 2009)	1.07
"Levodopa treatment did not affect sleep or lead to increased EDS in DLB patients."	( Levodopa use and sleep in patients with dementia with Lewy bodies. Burn, DJ; McKeith, IG; Minett, T; Molloy, S; O'Brien, JT, 2009)	2.52
"Levodopa treatment improved motor symptoms in three out of ten patients of group I and in eight out of nine patients of group II."	( Clinical and [123I]FP-CIT SPET imaging follow-up in patients with drug-induced parkinsonism. Antonini, A; Bovi, T; Fiaschi, A; Moretto, G; Ottaviani, S; Pasquin, I; Steinmayr, M; Tinazzi, M, 2009)	1.07
"Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group."	( Quantitative autoradiographic study on receptor regulation in the basal ganglia in rat model of levodopa-induced motor complications. Cao, X; Papa, SM; Qin, K; Xu, Y; Zhang, Z, 2009)	1.29
"Levodopa treatment in patients with Parkinson's disease (PD) is known to cause elevation in serum homocysteine levels. "	( The effect of levodopa treatment on cerebral hemodynamics in patients with Parkinson's disease: serial transcranial Doppler studies. Lee, KY; Lee, PH; Yong, SW, 2010)	2.16
"Levodopa treatment could have either beneficial or detrimental effects on brain functions modulated by DA according to disease progression."	( Dopaminergic modulation of amygdala activity during emotion recognition in patients with Parkinson disease. Azulay, JP; Blin, O; Delaveau, P; Fakra, E; Micallef-Roll, J; Salgado-Pineda, P; Witjas, T, 2009)	1.07
"The levodopa-treated MPTP-lesioned marmoset was used as a model of neuropsychiatric symptoms in PD patients."	( Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson's disease. Brotchie, JM; Fox, SH; Gomez-Ramirez, J; Huot, P; Johnston, T; Reyes, G; Visanji, N, 2010)	0.84
"Levodopa-treated MPTP monkeys developed dyskinesias while those that received levodopa+CI-1041 or levodopa+cabergoline did not."	( Changes of AMPA receptors in MPTP monkeys with levodopa-induced dyskinesias. Di Paolo, T; Gasparini, F; Gomez-Mancilla, B; Grégoire, L; Hoyer, D; Morissette, M; Ouattara, B, 2010)	1.34
"Levodopa-treated PD participants with LID (n = 38) received LEV 500 mg/day, were assessed, titrated to 1,000 mg/day and reassessed, before and after crossover."	( Levetiracetam for the management of levodopa-induced dyskinesias in Parkinson's disease. Konitsiotis, S; Peterson, D; Stathis, P; Tagaris, G, 2011)	1.37
"Levodopa treatment induced dyskinesias and did not modify the striatal expression of either VGlut1 or VGlut2."	( The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl) pyridine decreases striatal VGlut2 expression in association with an attenuation of L-DOPA-induced dyskinesias. Aguilar, E; Bonastre, M; Jiménez, A; Marin, C, 2011)	1.09
"Levodopa treatment in Parkinson's disease (PD) increases in serum homocysteine levels due to its metabolism via catechol O-methyltransferase. "	( Comparison of endothelial progenitor cells in Parkinson's disease patients treated with levodopa and levodopa/COMT inhibitor. Choi, Y; Hong, JY; Kim, HO; Kim, HS; Lee, JE; Lee, PH; Nam, HS; Sohn, YH, 2011)	2.03
"Levodopa treatment was initiated at age 10 months and resulted in a distinct motor improvement."	( Beneficial prenatal levodopa therapy in autosomal recessive guanosine triphosphate cyclohydrolase 1 deficiency. Boor, R; Brüggemann, N; Gillessen-Kaesbach, G; Hellenbroich, Y; Klein, C; Opladen, T; Schneider, SA; Sperner, J; Spiegler, J; Stephani, U, 2012)	1.42
"In levodopa-treated PD patients, adherence to ODDA therapy is suboptimal and strongly associated with the levodopa daily dose and the total number of drugs used to treat patients' medical conditions."	( Levodopa dosage determines adherence to long-acting dopamine agonists in Parkinson's disease. de la Fuente-Fernández, R; Prieto-Formoso, M; Santos-García, D, 2012)	2.44
"Levodopa treatment of Parkinson's disease is very effective, but many types of adverse events can complicate the disease course, especially dyskinesias. "	( Recurrent bilateral metatarsal "stress-and-insufficiency" fractures in a levodopa-treated young woman with Parkinson's disease. Daragon, A; Derrey, S; Lefaucheur, R; Maltête, D; Nicolau, J; Verdet, M, 2013)	2.06
"Levodopa treatment increased release of homocysteine on astrocytes culture media as well as in plasma and brain of PD animals."	( Elevated homocysteine by levodopa is detrimental to neurogenesis in parkinsonian model. Ahn, YH; Lee, PH; Paik, MJ; Park, HJ; Shin, JY; Sohn, YH, 2012)	1.4
"Levodopa-treated Parkinson's disease patients who had been treated with deprenyl for up to 7 years, compared with patients who were changed to a placebo after about 5 years, experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait."	( Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson's disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Fahn, S; Kieburtz, K; Lang, A; Langston, JW; LeWitt, P; Oakes, D; Olanow, CW; Penney, JB; Rudolph, A; Shoulson, I; Tanner, C, 2002)	1.3
"Levodopa treatment is useful and diagnosis may be done on fluctuant dystonia in the childhood."	( [Hereditary progressive levodopa sensible: Segawa's syndrome]. Corral, SM; Grippo, J; Grippo, T; La Fuente, A, )	1.88
"Levodopa treatment appears to have subtle detrimental effects on cognitive function in nondemented PD patients. "	( Effects of levodopa on motor sequence learning in Parkinson's disease. Carbon, M; Dhawan, V; Edwards, C; Eidelberg, D; Feigin, A; Fukuda, M; Ghez, C; Ghilardi, MF; Margouleff, C, 2003)	2.15
"Levodopa-treated patients showed significantly higher IL-15 and RANTES circulating levels with respect to healthy controls and higher, although not significantly, levels with respect to untreated patients."	( Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinson's disease. Basile, G; Di Pasquale, G; Epifanio, A; Ferlazzo, B; Gangemi, S; Merendino, RA; Morgante, L; Nicita-Mauro, V, 2003)	1.44
"Levodopa treatment did not significantly change the plasma lipoprotein oxidation but LD monotherapy tended to result in an increase of autooxidation and in a decrease of plasma antioxidants with significance for ubiquinol-10."	( Plasma and CSF markers of oxidative stress are increased in Parkinson's disease and influenced by antiparkinsonian medication. Arlt, S; Beisiegel, U; Buhmann, C; Kontush, A; Möller-Bertram, T; Oechsner, M; Sperber, S; Stuerenburg, HJ, 2004)	1.04
"Levodopa-treated Parkinson's disease is often complicated by the occurrence of motor fluctuations, which can be predictable ('wearing-off') or unpredictable ('on-off'). "	( Presynaptic mechanisms of motor fluctuations in Parkinson's disease: a probabilistic model. Calne, DB; de la Fuente-Fernández, R; Mak, E; Schulzer, M; Stoessl, AJ, 2004)	1.77
"Levodopa, the major treatment for patients with Parkinson's disease, has been shown to induce a variety of compensatory effects, including facilitation of sprouting by dopaminergic neurons, in experimental animals with lesions leading to denervation of the striatum. "	( Differential gene expression induced by chronic levodopa treatment in the striatum of rats with lesions of the nigrostriatal system. Delfino, MA; Ferrario, JE; Gershanik, O; Mourlevat, S; Murer, MG; Raisman-Vozari, R; Ruberg, M; Stefano, A; Taravini, IR, 2004)	2.02
"Levodopa, the treatment of choice, offers initial improvement, but causes long term important complications."	( [Influence of levodopa on cognition of idiopathic Parkinson's disease]. Alonso-Prieto, E; Michel-Esteban, E; Palmero-Soler, E; Trujillo-Matienzo, C, 2004)	1.41
"Levodopa treatment has been shown to increase plasma homocysteine levels in Parkinson's disease (PD) patients and this may lead to an increased risk for coronary arterial diseases. "	( The COMT inhibitor, entacapone, reduces levodopa-induced elevations in plasma homocysteine in healthy adult rats. Helkamaa, T; Larjonmaa, H; Nissinen, E; Nissinen, H; Rauhala, P; Reenilä, I; Väänänen, A, 2005)	2.04
"Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). "	( The controversy concerning plasma homocysteine in Parkinson disease patients treated with levodopa alone or with entacapone: effects of vitamin status. Hauser, RA; Merlin, LR; Sullivan, KL; Wecker, L; Zesiewicz, TA, )	1.8
"Levodopa, the main treatment for this condition, was first used for PD more than 40 years ago and today it still is the most powerful treatment for this disease."	( [Levodopa for Parkinson's disease: What have we learned?]. Chaná C, P; Juri C, C, 2006)	1.97
"Levodopa-treated patients (N = 37) were examined both in a practically defined 'OFF' as well as in the 'ON' state."	( Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia. Berendse, HW; Bosboom, JL; Deijen, JB; Stam, CJ; Stoffers, D; Wolters, EC, 2007)	1.06
"Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed."	( Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition. Angelopoulos, E; Boufidou, F; Evangelopoulos, ME; Kararizou, E; Nikolaou, C; Rentzos, M; Triantafyllou, NI; Vassilopoulos, D, 2008)	1.35
"Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations."	( Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform. Grabowski, J; Green, C; Moeller, FG; Mooney, ME; Schmitz, JM; Stotts, AL, 2008)	2.51
"Levodopa treatment was initially effective in 95% of the patients but the response decreased with time."	( Long-term Parkinson's disease--time for optimism. Djaldetti, R; Melamed, E; Sthneer, S; Yust-Katz, S, )	0.85
"Levodopa treatment did not have any significant effect on the enkephalin bindings."	( Brain enkephalin receptors in Parkinson's disease. Koskinen, V; Laakso, K; Lönnberg, P; Rinne, JK; Rinne, JO; Rinne, UK; Tenovuo, O, 1983)	0.99
"Levodopa treatment improves significantly not only the parkinsonian disability but also the mortality rate. "	( Problems associated with long-term levodopa treatment of Parkinson's disease. Rinne, UK, 1983)	1.99
"Levodopa treatment alleviated the parkinsonian symptoms to a considerable degree and substantially improved the quality of life of the parkinsonian patients."	( Long-term responses of Parkinson's disease to levodopa therapy. Marttila, R; Rinne, UK; Siirtola, T; Sonninen, V, 1980)	1.24
"Oral levodopa treatment remains the most efficacious treatment of Parkinson's disease, but the majority of patients treated with a levodopa monotherapy for more than 5 years will develop fluctuations and/or dyskinesias. "	( Current strategies in the drug treatment of advanced Parkinson's disease--new modes of dopamine substitution. Poewe, W; Schelosky, L, 1993)	0.8
"Levodopa treatment might change the dopaminergic and serotoninergic neuronal systems, but not the noradrenergic or adrenergic neuronal systems, in CNS of PD patients."	( Monoamines and their metabolites in plasma and lumbar cerebrospinal fluid of Chinese patients with Parkinson's disease. Cheng, FC; Chia, LG; Kuo, JS, 1993)	1.01
"Levodopa treatment for PD may therefore constitute an additional challenge for the defective apoptosis-inhibiting systems in the nigrostriatal neurons."	( Levodopa induces apoptosis in cultured neuronal cells--a possible accelerator of nigrostriatal degeneration in Parkinson's disease? Barzilai, A; Melamed, E; Offen, D; Shirvan, A; Zilkha-Falb, R; Ziv, I, 1997)	2.46
"Levodopa treatment had no effect on the measured autonomic responses."	( Selegiline diminishes cardiovascular autonomic responses in Parkinson's disease. Myllylä, VV; Sotaniemi, K; Suominen, K; Tolonen, U; Turkka, J, 1997)	1.02
"Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout."	( Long-duration response to levodopa influences the pharmacodynamics of short-duration response in Parkinson's disease. Aguglia, U; Colao, R; Gambardella, A; Montesanti, R; Oliveri, RL; Quattrone, A; Rizzo, M; Zappia, M, 1997)	1.32
"Levodopa/benserazide treatment significantly improved motor aspects of object retrieval performance but did not significantly improve cognition."	( Effects of the nicotinic acetylcholine receptor agonist SIB-1508Y on object retrieval performance in MPTP-treated monkeys: comparison with levodopa treatment. Lloyd, GK; Menzaghi, F; Schneider, JS; Van Velson, M, 1998)	1.22
"In levodopa-treated animals, 5-HTP concentrations were moderately correlated (r = 0.679) between striatum and CSF, while weak correlations were present between striatal and CSF concentrations of both serotonin and 5-HIAA."	( Influence of repeated levodopa administration on rabbit striatal serotonin metabolism, and comparison between striatal and CSF alterations. Camp, DM; DeMaggio, AJ; Havaich, MK; Juneau, PL; LeWitt, PA; Loeffler, DA; Matson, WR; Milbury, PE, 1998)	1.13
"Levodopa treatment is used to reduce rigidity and bradykinesia in Parkinson's disease (PD). "	( Handwriting and speech changes across the levodopa cycle in Parkinson's disease. Brookshire, RH; Poluha, PC; Teulings, HL, 1998)	2.01
"Levodopa treatment in Parkinson's disease has been suggested to contribute to disease progression through free radical generation. "	( Time-dependent effects of levodopa on regional brain dopamine metabolism and lipid peroxidation. Arnold, LA; Camp, DM; Hyland, K; Juneau, PL; LeWitt, PA; Loeffler, DA, 1998)	2.04
"Levodopa/benserazide treatment was well tolerated and safe."	( Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial. Benes, H; Kazenwadel, J; Kohnen, R; Kummer, J; Kurella, B; Selzer, R, 1999)	1.33
"Levodopa treatment did not unmask significant chorea."	( Late onset levodopa responsive Huntington's disease with minimal chorea masquerading as Parkinson plus syndrome. Andrews, TC; Brooks, DJ; Chaudhuri, KR; Clough, C; Hu, MT; Reuter, I, 2000)	1.42
"Levodopa treatment significantly increased the expression of striatal MT-III mRNA in the non-lesioned side, but showed no significant effect in the 6-OHDA-lesioned side."	( Expression of metallothionein-III mRNA and its regulation by levodopa in the basal ganglia of hemi-parkinsonian rats. Asanuma, M; Higashi, Y; Miyazaki, I; Nakanishi, T; Ogawa, N; Sogawa, CA; Tanaka, KI, 2000)	1.27
"Levodopa/DDI long-term treatment contributes to altered levels of substrates of the O-methylation cycle in PP."	( Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson's disease. Fowler, B; Hauptmann, B; Kuhn, W; Müller, T; Woitalla, D, 2001)	1.03
"Levodopa treatment, alone or in combination with two different dopa-decarboxylase inhibitors, benserazide and carbidopa, does not modify the renin response to posture or to frusemide."	( Effects of levodopa alone and in combination with dopa-decarboxylase inhibitors on plasma renin activity in patients with Parkinson's disease. Dessi'-Fulgheri, P; Glorioso, N; Monaco, F; Rappelli, A; Tedde, R, 1978)	1.37
"The levodopa treatment was repeated each day during one week."	( Recovery from experimental paraplegia after levodopa administration. Popovic, P; Popovic, V; Schaffer, R, 1976)	1
"Levodopa treatment corrected these values to the level of controls, whereas the amount of phosphatidylserine was decreased."	( Interaction between dopamine and phospholipids. Studies of the substantia nigra in Parkinson disease patients. Pelliniemi, TT; Riekkinen, P; Rinne, UK; Sonninen, V, 1975)	0.98
"Levodopa-treated patients were able to produce more correct responses, but were still unable to maintain the correct responses to produce more correct concepts than non-levodopa-treated patients."	( Parkinsonism: effects of levodopa treatment on concept formation. Bowen, FP; Burns, MM; Kamienny, RS; Yahr, M, 1975)	1.28
"The levodopa treatment was repeated every day for 6 days."	( Levodopa-enhanced recovery from paralysis induced by air embolism. Popovic, P; Popovic, V; Schaffer, R, 1976)	2.18
"Levodopa is the treatment of choice in Parkinson's disease, but a high percentage of patients develop complications in the response, including fluctuations, after some years of treatment. "	( [Effect of a controlled low-protein diet on the pharmacological response to levodopa and on the plasma levels of L-dopa and amino acids in patients with Parkinson's disease]. Casarejo, MJ; de Yébenes, JG; de Yébenes, MJ; Jiménez, A; Martín del Río, R; Mena, MA; Morales, B; Sanchís, G; Tabernero, C, )	1.8
"The levodopa-treated patients stopped taking levodopa before the test."	( Slowing of high-speed memory scanning in Parkinson's disease is related to the severity of parkinsonian motor symptoms. Berger, W; Bitschnau, W; Karamat, E; Kemmler, GW; Poewe, W; Ransmayr, G; Schmidhuber-Eiler, B, 1990)	0.76
"Levodopa/carbidopa treatment decreased significantly prolactin and thyrotropin levels in serum but none of the additional treatments changed this action."	( Effect of acute levodopa on brain catecholamines after selective MAO and COMT inhibition in male rats. Kaakkola, S; Männistö, PT; Toivonen, M; Törnwall, M; Tuomainen, P, 1990)	1.35
"With levodopa treatment: The duration of illness at each stage of severity was 3 to 5 years longer; at every duration of illness, death and disability were reduced 1.5- to 3-fold, except in patients whose treatment had been delayed; abnormal involuntary movements that interfered with function occurred in 24% of patients; severe fluctuations that required rescheduling of activities occurred in 29% of patients; severe AIMs and fluctuations were rare during the first 3 years of treatment, but remained constant thereafter, without progressive increase; prevalence of severe fluctuations was related only to age of onset of disease: If under 50, severe fluctuations developed in 66%, if age 50 to 59 at onset, they developed in 30%, if over age 60, in only 6%; average age at death was 6 years older; and observed/expected mortality was 1.2, not significantly different from the unaffected population."	( Parkinson's disease: progression and mortality. Hoehn, MM, 1987)	0.73
"24 levodopa pretreated patients with advanced parkinsonism were split into two equal groups receiving mesulergine or bromocriptine respectively as an adjuvant therapy. "	( Mesulergine and bromocriptine in long-term treatment of advanced parkinsonism. Baas, H; Fischer, PA; Japp, G; Schneider, E, 1985)	0.89
"Treatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). "	( Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study. Baille, G; Blaise, AS; Carrière, N; Defebvre, L; Devos, D; Dujardin, K; Grolez, G; Kreisler, A; Kyheng, M; Moreau, C; Mutez, E; Seguy, D, 2020)	1.21
"Treatment with levodopa increases pain thresholds in patients with PD. "	( Current Status of Pain Management in Parkinson's Disease. Bruno, V; Farcy, N; Karnik, V; Zamorano, C, 2020)	0.91
"Treatment with levodopa-carbidopa intestinal gel (LCIG) was introduced at age 57."	( [Optimal dose of levodopa-carbidopa intestinal gel in the treatment of diphasic dyskinesia and freezing of gait]. Fujioka, S; Komorita, S; Mishima, T; Nishida, A; Okajima, M; Tsuboi, Y, 2021)	1.3
"The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy."	( Randomized, placebo-controlled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson's disease (EASE LID 3). Azulay, JP; Eggert, K; Ehret, R; Felt, L; Hauser, RA; Isaacson, S; Oertel, W; Pahwa, R; Stempien, MJ; Tanner, CM; Trenkwalder, C, 2017)	1.01
"Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts."	( Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication. Brown, P; Herz, DM; Kühn, AA; Pogosyan, A; Tan, H; Tinkhauser, G, 2017)	0.79
"Treatment of levodopa (L-dopa)-induced motor fluctuations is still an unmet medical need."	( Adjunctive Therapies in Parkinson's Disease: How to Choose the Best Treatment Strategy Approach. Fabbri, M; Ferreira, JJ; Rosa, MM, 2018)	0.83
"Treatment with levodopa enhances functional recovery after experimental stroke but its mechanisms of action are elusive. "	( Dopamine receptor activation increases glial cell line-derived neurotrophic factor in experimental stroke. Kuric, E; Ruscher, K; Wieloch, T, 2013)	0.74
"Treatment with levodopa/benserazide completely recovered T-helper cell depletion in animals subjected to tMCAO whereas T-cell associated cytokines remained unaffected after stroke, however, cytokines were downregulated in levodopa treated sham operated animals."	( Reversal of stroke induced lymphocytopenia by levodopa/benserazide treatment. Kuric, E; Ruscher, K, 2014)	1
"Treatment with levodopa relieved his symptoms and resulted in a height increase."	( Growth hormone deficiency in a dopa-responsive dystonia patient with a novel mutation of guanosine triphosphate cyclohydrolase 1 gene. Chen, WJ; Lin, MT; Lin, X; Lin, Y; Wang, DN; Wang, N, 2015)	0.76
"Treatment with levodopa typically improves these three symptoms."	( Dopa-Responsive Dystonia and gait analysis: A case study of levodopa therapeutic effects. Arsenault, L; Broussolle, E; Delporte, L; Luauté, J; Mizuno, K; Rebour, R; Revol, P; Rossetti, Y, 2015)	1
"Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state."	( Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus. Boelmans, K; Buhmann, C; Engel, AK; Gerloff, C; Gulberti, A; Hamel, W; Koeppen, JA; Moll, CK; Schneider, TR; Westphal, M; Zittel, S, 2015)	0.76
"IP treatment with levodopa also produced contralateral rotation in PD induced rats, and showed anti-Parkinson-like action."	( CART modulates the effects of levodopa in rat model of Parkinson's disease. Kokare, DM; Shelkar, GP; Subhedar, NK; Upadhya, MA, 2016)	1.05
"Treatment with levodopa led to symptom control."	( Holmes' tremor as a delayed complication of thalamic stroke. Cristovam, Rdo A; Fussiger, H; Marrone, AC; Marrone, LC; Martins, WA; Taietti, MZ; Vedana, VM, 2016)	0.77
"Treatment with levodopa and thalamic stereotactic lesional surgery seems to be effective."	( Holmes tremor: Clinical description, lesion localization, and treatment in a series of 29 cases. Calandra, C; Calvo, DS; Cersosimo, MG; Fernandez Pardal, MM; Folgar, SS; Giannaula, RJ; Giugni, JC; Micheli, FE; Paviolo, JP; Pellene, LA; Raina, GB; Tkachuk, VA; Tschopp, AL; Uribe Roca, MC; Velez, M; Zuñiga Ramirez, C, 2016)	0.77
"Treatment with levodopa was initiated in order to treat her neurological problem and progressive remission of the skin lesions was noted."	( Resolution of inverse psoriasis after treatment with levodopa for Parkinson's disease. Arjona Aguilera, C; Espinosa Rosso, R; Jiménez Gallo, D; Linares Barrios, M; Rojo Suárez, N, 2017)	1.04
"A pretreatment with Levodopa+Benserazide for two or seven days induced an additional decrease in Walking after rEMS."	( Levodopa enhances immobility induced by spinal cord electromagnetic stimulation in rats. de Andrade, LM; Gondim, FA; Pitcher, MR; Rola, FH; Sales, PM, 2016)	2.19
"Treatment with levodopa/DDCI and entacapone extends the half-life of levodopa, avoiding deep troughs in levodopa plasma levels and providing more continuous delivery of levodopa to the brain."	( Levodopa/DDCI and entacapone is the preferred treatment for Parkinson's disease patients with motor fluctuations in routine practice: a retrospective, observational analysis of a large French cohort. Bourdeix, I; Damier, P; Rerat, K; Viallet, F; Ziegler, M, 2008)	2.13
"Treatment with levodopa/carbidopa/entacapone resulted in significantly greater improvements in PDQ-8 scores compared to treatment with levodopa/carbidopa (mean difference 1.4 points, P = 0.021)."	( Quality of life in early Parkinson's disease treated with levodopa/carbidopa/entacapone. Fung, VS; Herawati, L; Wan, Y, 2009)	0.94
"Treatment with levodopa alone did not change rCBF, whereas it increased basal ganglion DAT activity in the most affected hemisphere."	( Complementary acupuncture in Parkinson's disease: a spect study. Huang, Y; Jiang, X; Wik, G; Zhuo, Y, 2010)	0.7
"Treatment with Levodopa/Carbidopa resulted in striking clinical improvement, with age-appropriate development at follow-up at 6 years."	( Clinical and biochemical characterization of patients with early infantile onset of autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia. Hinz, AB; Hoffmann, G; Hörster, F; Klein, C; Neidhardt, K; Opladen, T; Wolf, N, 2011)	0.71
"Treatment with levodopa/benserazide significantly improved the recovery of sensorimotor function after transient occlusion of the middle cerebral artery without affecting the infarct volume. "	( Levodopa treatment improves functional recovery after experimental stroke. Kuric, E; Ruscher, K; Wieloch, T, 2012)	2.17
"Treatment with levodopa or dopamine agonists is the first-line therapy for RLS; however, there are limited data on treatment in pregnancy."	( Pregnancy outcome following use of levodopa, pramipexole, ropinirole, and rotigotine for restless legs syndrome during pregnancy: a case series. Dostal, M; Schaefer, C; Sobesky, J; Weber-Schoendorfer, C, 2013)	1.01
"Treatment with levodopa increases postural sway abnormalities, whereas treatment with deep brain stimulation improves postural sway."	( Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease. Chiari, L; Horak, FB; Rocchi, L, 2002)	0.93
"Treatment with levodopa ameliorates but usually does not normalize symptoms."	( Tyrosine hydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsive dystonia. Assmann, B; Bräutigam, C; de Klerk, JB; Dionisi-Vici, C; Häussler, M; Hoffmann, GF; Naumann, M; Steenbergen-Spanjers, GC; Strassburg, HM; Wevers, RA, 2003)	0.66
"Treatment with levodopa led to marked improvement in his neurological status and quality of life."	( Hereditary spastic paraplegia associated with dopa-responsive parkinsonism. Cersósimo, MG; Micheli, F; Zúñiga Ramírez, C, 2006)	0.67
"Treatment with levodopa improved her symptoms considerably but incompletely."	( Adult-onset dystonia: atypical manifestation of Segawa disease. Meinck, HM; Regula, JU; Thoden, U, 2007)	0.68
"Treatment with levodopa did not have any significant effect on the binding of 3H-enkephalins."	( Brain receptor changes in Parkinson's disease in relation to the disease process and treatment. Laakso, K; Laihinen, A; Lönnberg, P; Rinne, JK; Rinne, JO; Rinne, UK, 1983)	0.61
"In untreated or levodopa-treated patients, there was considerable improvement of akinesia, rigidity, and tremor; on-off symptoms also improved in the levodopa-treated patients."	( Treatment of Parkinson's disease with 8-alpha-amino-ergoline, CU 32-085. Fischer, PA; Hubener, K; Schneider, E, 1983)	0.6
"Treatment with levodopa was of clear benefit."	( Benign paroxysmal tonic upgaze of childhood with ataxia. A neuro-ophthalmological syndrome of familial origin? Campistol, J; Garaizar, C; Prats, JM, 1993)	0.63
"Treatment with levodopa and dopa decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in combination with selegiline (arm 2)."	( Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. Lees, AJ, 1995)	0.89
"Treatment with levodopa, a precursor of dopamine, initially ameliorates the clinical manifestations of PD."	( Altered thalamic response to levodopa in Parkinson's patients with dopa-induced dyskinesias. Black, KJ; Carl, JL; Hershey, T; McGee-Minnich, LA; Perlmutter, JS; Stambuk, MK, 1998)	0.93
"Treatment with levodopa produced substantial functional motor improvement with a 17 point reduction in the unified Parkinson's disease rating scale (UPDRS) motor subscale including reduction of tremor, bradykinesia, and postural instability."	( Levodopa responsive parkinsonism in an adult with Huntington's disease. Perlmutter, JS; Racette, BA, 1998)	2.08
"The treatment of levodopa-induced dyskinesias must be considered in regard to the subtype and the severity of dyskinesias, and the patient."	( Treating and preventing levodopa-induced dyskinesias: current and future strategies. Durif, F, 1999)	0.94
"Treatment with levodopa has resulted in a marked decrease in disease-associated mortality and morbidity."	( Maximizing the benefit:risk ratio of levodopa therapy in Parkinson's disease. Gottwald, MD, 1999)	0.92
"Treatment with levodopa was ineffective."	( Unsuccessful treatment with levodopa of a parkinsonian patient with calcification of the basal ganglia. Berendes, K; Dörstelmann, D, 1978)	0.89
"Treatment with levodopa did not induce significant alterations in the mean brain, mean hemispheric or regional flow values in these patients."	( Regional cerebral blood flow in parkinsonism. Measurement before and after levodopa. Bentin, S; Cooper, G; Lavy, S; Melamed, E, 1978)	0.83
"Treatment with levodopa makes these motor units accessible to activation and frequency control."	( Motor unit control in Parkinson's disease and the influence of levodopa. Jarcho, LW; Petajan, JH, 1975)	0.83
"Treatment with levodopa gives remarkable and durable results, but it must be continued indefinitely."	( [Dopa-sensitive dystonia]. Aicardi, J; Goutières, F; Rondot, P; Ziegler, M, 1992)	0.62
"Treatment with levodopa failed to modify tumoral progress."	( Impaired levodopa response in Parkinson's disease during melanoma therapy. Esteguy, M; Leiguarda, R; Merello, M; Perazzo, F, 1992)	1.04
"Treatment with levodopa induced an increase in interleukin-1 synthesis, and in IgM and IgA levels in plasma, which suggest a possible selective action on cells of the immune system."	( The immunological status in Parkinson's disease. Członkowska, A; Fiszer, U; Korlak, J; Piotrowska, K, 1991)	0.62
"Treatment with levodopa, 50 mg, and benserazide, 12.5 mg, three times a day was withdrawn from a 76-year-old woman with mild Parkinson's disease because she was experiencing intermittent confusion. "	( Neuroleptic malignant syndrome complicating levodopa withdrawal. Goldswain, PR; Harrison, WB; Reutens, DC, 1991)	0.9
"Treatment with levodopa, carbidopa and 5-hydroxytryptophan resulted in prompt neurological improvement."	( Successful long term therapy of biopterin deficiency. Pulmones, MT; Sansaricq, C; Snyderman, SE, 1987)	0.61
"Treatment with levodopa gave some relief of the parkinsonism symptoms in two patients but exacerbated or reactivated the dystonia."	( Parkinsonism following dystonia in three patients. Duvoisin, RC; Katchen, M, 1986)	0.61
"Oral treatment with levodopacarbidopa (1000/100 mg) or subcutaneous administration of apomorphine (1 mg) abolished the visually-triggered myoclonus, without modifying reflex myoclonus to electrical or tactile stimulation."	( Dopamine agonists suppress visual-cortical reflex myoclonus. Artieda, J; Luquin, MR; Martínez Lage, JM; Obeso, JA; Tuñón, T, 1985)	0.58

Toxicity

5 to 1 mg/day rasagiline in addition to levodopa is a safe and well-tolerated combination therapy. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam.

Excerpt	Reference	Relevance
" Additional adverse reactions including dyskinesias, "on-off" phenomena, and declining efficacy of levodopa were present in all patients."	( Early-morning dystonia. A late side effect of long-term levodopa therapy in Parkinson's disease. Melamed, E, 1979)	0.72
" The adverse effect reappeared in a more severe and prolonged form when she was treated one year later with levodopa in combination with the peripheral decarboxylase inhibitor Ro-4-4602."	( Prolonged symptoms of brain dysfunction--adverse effect of levodopa. Anggård, E; Samuelsson, K, 1976)	0.71
" LD50 values of three of these compounds were assessed after intraperitoneal administration with a special emphasis on interactions with drugs increasing catecholaminergic neurotransmission."	( Acute toxicity of three new selective COMT inhibitors in mice with special emphasis on interactions with drugs increasing catecholaminergic neurotransmission. Männistö, PT; Törnwall, M, 1991)	0.28
"001) on 'Sinemet CR4' although median (range) total daily dose of levodopa was increased from 700 (375-2525) to 800 (400-2800) mg without any increase in adverse effects."	( Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety. Bulling, MT; Burns, RJ; Wing, LM, 1991)	0.85
" Adverse effects were mild and transient and resolved with dosage manipulation or a divided dosage regimen."	( CV 205-502: safety, tolerance to, and efficacy of increasing doses in patients with Parkinson's disease in a double-blind, placebo crossover study. Gauger, LL; Olanow, CW; Werner, EG, 1989)	0.28
" Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry."	( Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa. Gilley, DW; Goetz, CG; Klawans, HL; Tanner, CM, 1989)	0.7
"8 nmol/mg for pirenzepine and 71 nmol/mg for chloroquine, a compound which has been described as provoking toxic side-effects in melanin-containing tissues and adjacent structures."	( Melanosome binding and oxidation-reduction properties of synthetic L-dopa-melanin as in vitro tests for drug toxicity. Debing, I; Ijzerman, AP; Vauquelin, G, 1988)	0.27
" L-DOPA was toxic for both DA and non-DA neurons."	( Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants. Casarejos, MJ; De Yébenes, JG; Mena, MA; Paíno, CL; Pardo, B, 1995)	0.29
" Furthermore, these findings suggest that patients on long-term L-DOPA therapy are potentially at risk from the toxic intermediates formed as a result of its autoxidation."	( L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation. Basma, AN; Geller, HM; Morris, EJ; Nicklas, WJ, 1995)	0.29
" Neither L-dopa nor MnCl2 alone was toxic at these concentrations, and cytotoxicity was completely abrogated by substitution of L-tyrosine for L-dopa."	( Fibroblasts that express aromatic amino acid decarboxylase have increased sensitivity to the synergistic cytotoxicity of L-dopa and manganese. Graham, DG; Linney, E; Montine, TJ; Underhill, TM, 1994)	0.29
"25 x 10(-4) M or larger, is toxic for the human neuroblastoma cell NB69."	( Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line. Fahn, S; García de Yébenes, J; Mena, MA; Pardo, B, 1993)	0.57
" While dysphagia is commonly encountered in patients with Parkinson's disease, the observed succession of drug discontinuation and resolution of obstruction in this case suggests an as yet rarely described side effect of levodopa."	( [Reversible esophageal dysfunction as a side effect of levodopa]. Frank, M; Kellner, H; Liegl, U; Zoller, WG, 1996)	0.73
" Mesencephalic glia therefore produced soluble factors which are neurotrophic for dopamine neurones, and which protect these neurones from the toxic effects of L-DOPA."	( Glia conditioned medium protects fetal rat midbrain neurones in culture from L-DOPA toxicity. Carazo, A; Casarejos, MJ; García de Yébenes, J; Mena, MA; Paino, CL, 1996)	0.29
" Motor side effects and adverse events were recorded at each regular clinic visit."	( Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study. Blümner, E; Danielczyk, W; Gerlach, M; Kaiser, HJ; Kraus, PH; Letzel, H; Przuntek, H; Riederer, P; Uberla, K; Welzel, D, 1996)	0.52
" We have assessed the toxic effects of dopamine and L-DOPA toward catecholaminergic neuroblastoma SH-SY5Y cells and whether R(-)-deprenyl and several structurally related compounds possess antioxidant effects in this system."	( R(-)-deprenyl potentiates dopamine-induced cytotoxicity toward catecholaminergic neuroblastoma SH-SY5Y cells. Lai, CT; Yu, PH, 1997)	0.3
" Hydrogen peroxide would be converted to more toxic hydroxyl free radicals."	( Dopamine- and L-beta-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Effects of oxidative stress and antioxidative factors. Lai, CT; Yu, PH, 1997)	0.3
" Drugs used to treat PD, such as levodopa, offer symptomatic relief but often have neuropsychiatric adverse effects, most prominently psychosis and delirium."	( Neuropsychiatric adverse effects of antiparkinsonian drugs. Characteristics, evaluation and treatment. Camicioli, R; Ganzini, L; Young, BK, 1997)	0.58
" There is abundant evidence that levodopa is toxic to embryonic nigral DA neurons in both cell culture and neural grafting models."	( Comparison of neurotoxicity following repeated administration of l-dopa, d-dopa and dopamine to embryonic mesencephalic dopamine neurons in cultures derived from Fisher 344 and Sprague-Dawley donors. Alexander, T; Roth, RH; Sladek, CD; Sortwell, CE; Steece-Collier, K, )	0.41
" Adverse responses to Sinemet treatment alone in parkinsonian animals included vomiting, dykinesias, dystonias, and stereotypic movements."	( Glial cell line-derived neurotrophic factor-levodopa interactions and reduction of side effects in parkinsonian monkeys. Collins, F; Gash, DM; Hilt, D; Kryscio, R; Lapchak, PA; Lebel, C; Miyoshi, Y; Ovadia, A; Zhang, Z, 1997)	0.56
" The principal adverse events were levodopa-related, but these were generally mild or moderate."	( Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group. Bailey, P; Deptula, D; Dorflinger, E; Kurth, M; LeWitt, P; Pedder, S; Shulman, LM; Waters, CH, 1997)	0.57
" Pretreatment with rotenone significantly augmented the toxic effect of L-DOPA on DA neurons."	( Metabolic inhibition enhances selective toxicity of L-DOPA toward mesencephalic dopamine neurons in vitro. Itakura, T; Nakai, K; Nakao, N, 1997)	0.3
" These results suggest that T-794 is an effective and particularly safe antidepressant and that it may make an important contribution in the treatment of depressive disorders."	( In vivo characterization of T-794, a novel reversible inhibitor of monoamine oxidase-A, as an antidepressant with a wide safety margin. Iwata, H; Katayama, T; Kato, M; Matsuoka, Y; Narita, H; Yamamura, M, 1998)	0.3
"Whether a drug such as levodopa, which is prescribed for long periods, may be toxic is a legitimate and even indispensable question."	( Levodopa: is toxicity a myth? Agid, Y, 1998)	2.05
" The principal adverse events were levodopa-related, but these were generally mild or moderate."	( Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. Tolcapone Stable Study Group. Bailey, P; Deptula, D; Dorflinger, E; Kurth, M; LeWitt, P; Pedder, S; Shulman, LM; Waters, CH, 1998)	0.58
" In early therapy, the emergent adverse experiences more common with the ropinirole group compared with placebo were nausea, somnolence, leg edema, abdominal pain, vomiting, dyspepsia, and hallucinations."	( The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson's disease. Brooks, DJ; Brunt, E; Fuell, D; Korczyn, A; Poewe, W; Quinn, NP; Rascol, O; Schrag, AE; Stocchi, F, )	0.13
" However, levodopa does not appear to be toxic to the development of fetal nigral neurons or to the survival of fetal cell transplants."	( Levodopa neurotoxicity: experimental studies versus clinical relevance. Brin, MF; Jenner, PG, 1998)	2.15
" As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors."	( Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. Heinonen, EH; Myllylä, V, 1998)	0.3
" Such toxic effects of levodopa can be blocked by co-treatment with antioxidants, particularly thiol-containing compounds."	( Levodopa toxicity and apoptosis. Barzilai, A; Djaldetti, R; Melamed, E; Offen, D; Shirvan, A; Ziv, I, 1998)	2.05
"Bilateral pallidal DBS is safe and efficient in patients who have levodopa-responsive parkinsonism with severe fluctuations."	( Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review. Assal, G; Fankhauser, H; Favre, J; Ghika, J; Ghika-Schmid, F; Villemure, JG, 1998)	0.75
" Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings."	( Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study. Oertel, WH; Pinter, MM; Pogarell, O, 1999)	0.3
" The adverse event profile disclosed a high tolerability."	( Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study. Oertel, WH; Pinter, MM; Pogarell, O, 1999)	0.3
" L-DOPA pretreatment did not significantly alter any of the toxic effects of the amphetamine."	( Neurotoxic effects of amphetamine plus L-DOPA. Halladay, AK; Myers, CS; Wagner, GC; Widmer, DA, 1999)	0.3
" The introduction of levodopa therapy is often delayed, however, because of the fear that it might be toxic for the remaining dopaminergic neurons, and thus accelerate the deterioration of the patient's condition."	( Levodopa in Parkinson's disease: neurotoxicity issue laid to rest? Gershanik, O; Murer, MG; Raisman-Vozari, R, 1999)	2.07
" Adverse effects were minor or transient."	( [Efficacy and safety of posteroventral pallidotomy for the treatment of advanced Parkinson's disease]. Ferrer, E; Molinuevo, JL; Nobbe, FA; Rumià, J; Tolosa, E; Valldeoriola, F, 2000)	0.31
"Microelectrode guided unilateral pallidotomy is an effective and safe procedure to improve contralateral motor symptoms in Parkinson's disease, being specially useful for the treatment of l-dopa induced dyskinesias."	( [Efficacy and safety of posteroventral pallidotomy for the treatment of advanced Parkinson's disease]. Ferrer, E; Molinuevo, JL; Nobbe, FA; Rumià, J; Tolosa, E; Valldeoriola, F, 2000)	0.31
" The dyskinesia develops over a period of exposure to L-dopa and is related to the dosage, therefore, the cause may involve inductive changes that produce toxic levels of metabolites, interfering with dopamine (DA) neurotransmission."	( Effects of dopamine metabolites on locomotor activities and on the binding of dopamine: relevance to the side effects of L-dopa. Charlton, CG; Crowell, B, 2000)	0.31
" These advantages contrasted with a need for more intensive postoperative monitoring and a higher incidence of adverse events related to levodopa withdrawal."	( Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Allert, N; Freund, HJ; Sturm, V; Voges, J; Volkmann, J; Weiss, PH, 2001)	0.51
"L-dopa may be toxic to dopamine neurons, possibly due to catechol-autoxidation."	( COMT-dependent protection of dopaminergic neurons by methionine, dimethionine and S-adenosylmethionine (SAM) against L-dopa toxicity in vitro. Bottiglieri, T; Bressman, S; Di Rocco, A; Prikhojan, A; Rempel, N; Werner, P; Yahr, MD, 2001)	0.31
" High concentrations of levodopa are toxic in vitro."	( Catechol-O-methyltransferase decreases levodopa toxicity in vitro. Galili-Mosberg, R; Melamed, E; Offen, D; Panet, H, )	0.71
" All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters."	( Twelve-month safety of entacapone in patients with Parkinson's disease. Haapaniemi, H; Kultalahti, ER; Leinonen, M; Myllylä, VV, 2001)	0.31
"L-3,4-Dihydroxyphenylalanine (L-DOPA) is a common and effective treatment for Parkinson's disease, but dyskinesia continues to be a serious adverse effect with chronic use."	( Behavioral activity and stereotypy in rats induced by L-DOPA metabolites: a possible role in the adverse effects of chronic L-DOPA treatment of Parkinson's disease. Akiyama, A; Nakazato, T, 2002)	0.31
"Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit."	( Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Deuschl, G; Gordin, A; Kultalahti, ER; Leinonen, M; Poewe, WH, 2002)	0.82
" However, L-DOPA has been suggested to be toxic to dopamine (DA) neurons and perhaps contribute to the progression of the disease."	( L-DOPA does not cause neurotoxicity in VMAT2 heterozygote knockout mice. Di Monte, DA; McCormack, AL; Miller, GW; Reveron, ME; Savelieva, KV; Tillerson, JL, 2002)	0.31
" However, the metabolites containing methoxy residue at position 3 failed to show a toxic effect in the SH-SY5Y cells."	( Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive quinone generation in neuroblastoma cells. Asanuma, M; Emdadul Haque, M; Higashi, Y; Miyazaki, I; Ogawa, N; Tanaka, K, 2003)	0.32
" In conclusion, STN lesioning is a safe and very effective procedure to treat PD and probably an underutilized operation for those who can not afford the costs of DBS."	( Unilateral subthalamic nucleus lesioning: a safe and effective treatment for Parkinson's disease. da Silva, DJ; Vilela Filho, O, 2002)	0.31
"To assess whether polymorphisms in the dopamine receptor genes and in the dopamine transporter gene (DAT ) are predictors of adverse effects of L -dopa."	( L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Brockmöller, J; Gasser, T; Grapengiesser, A; Hofer, A; Kaiser, R; Kupsch, A; Roots, I, 2003)	0.32
" The entire coding and promoter regions of the DRD2 gene of 48 patients with early and severe appearance of adverse effects from L -dopa treatment and of eight never-afflicted patients were sequenced."	( L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Brockmöller, J; Gasser, T; Grapengiesser, A; Hofer, A; Kaiser, R; Kupsch, A; Roots, I, 2003)	0.32
"The polymorphisms of DRD2, DRD3, and DRD4 were not associated with the risk to develop adverse effects of L -dopa."	( L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Brockmöller, J; Gasser, T; Grapengiesser, A; Hofer, A; Kaiser, R; Kupsch, A; Roots, I, 2003)	0.32
"Genetic variations of the DRD2, DRD3, and DRD4 do not influence the occurrence of L -dopa-induced adverse effects."	( L -dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Brockmöller, J; Gasser, T; Grapengiesser, A; Hofer, A; Kaiser, R; Kupsch, A; Roots, I, 2003)	0.32
"Dopamine (DA)- or L-dihydroxyphenylalanine-(L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reactions induced by long-term L-DOPA therapy but also in the pathogenesis of Parkinson's disease."	( Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease. Asanuma, M; Miyazaki, I; Ogawa, N, 2003)	0.32
"4%) discontinued treatment due to adverse events (AEs) by the end of the extension phase."	( Efficacy and safety of levodopa with entacapone in Parkinson's disease patients suboptimally controlled with levodopa alone, in daily clinical practice: an international, multicentre, open-label study. Bernhard, G; Emre, M; Gershanik, O; Sauer, D, 2003)	0.63
" Safety and tolerability were evaluated by treatment-emergent adverse event reports, clinical laboratory test results (blood chemistry, hematology, and urinalysis), vital signs, and electrocardiograms."	( Efficacy, safety, and tolerability of pramipexole in untreated and levodopa-treated patients with Parkinson's disease. Lu, CS; Mok, V; Shan, DE; Tsoi, TH; Wong, KS; Yang, CC, 2003)	0.56
"Adopting the randomized double-blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the treated group, who already received anti-Parkinsonism treatment but showing decreased response to Medopa and Artane and with obvious adverse reaction, was observed and controlled by 30 patients treated by adding placebo."	( [Clinical observation on the efficacy enhancing and toxicity attenuating effect of nuzhen yangyin granule to the anti-parkinsonism therapy mainly with Medopa]. Hu, XJ; Yang, XG; Yang, XS, 2003)	0.32
" NYG also showed markedly effective in reducing the adverse reactions of Medopa and Artane on digestive, neuro-psychiatric and cardiovascular system."	( [Clinical observation on the efficacy enhancing and toxicity attenuating effect of nuzhen yangyin granule to the anti-parkinsonism therapy mainly with Medopa]. Hu, XJ; Yang, XG; Yang, XS, 2003)	0.32
" In this short-term study, CEP-1347 was safe and well tolerated."	( The safety and tolerability of a mixed lineage kinase inhibitor (CEP-1347) in PD. , 2004)	0.32
" Safety assessments included monitoring adverse events, and the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination."	( Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. Cullen, EI; Hahne, WA; Kirby, L; Kumar, D; Okereke, CS; Pratt, RD, 2004)	0.58
" The number of PD patients who experienced at least one adverse event during the study (13/25) was higher when they received donepezil HCl than when they received placebo (5/25), but was the same as healthy subjects who received donepezil HCl only (13/26)."	( Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. Cullen, EI; Hahne, WA; Kirby, L; Kumar, D; Okereke, CS; Pratt, RD, 2004)	0.58
" Co-administration of the two drugs led to a small increase in adverse events compared with administration of levodopa/carbidopa alone in PD patients."	( Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. Cullen, EI; Hahne, WA; Kirby, L; Kumar, D; Okereke, CS; Pratt, RD, 2004)	0.79
" Assessments included tolerability measures, adverse events profile, the disease-specific quality of life instrument PDQ-39, UPDRS parts II, III, and question 39 and investigator and patient global clinical assessments."	( An open-label evaluation of the tolerability and safety of Stalevo (carbidopa, levodopa and entacapone) in Parkinson's disease patients experiencing wearing-off. Guarnieri, M; Hubble, J; Koller, W; Rabinowicz, AL; Silver, D, 2005)	0.56
"14 subjects (8%) discontinued treatment with Stalevo, of which 12 (7%) were due to adverse events."	( An open-label evaluation of the tolerability and safety of Stalevo (carbidopa, levodopa and entacapone) in Parkinson's disease patients experiencing wearing-off. Guarnieri, M; Hubble, J; Koller, W; Rabinowicz, AL; Silver, D, 2005)	0.56
" This toxic effect was demonstrated both in vitro and in vivo in several models but the concentrations required to induce it are significantly higher than those needed to inhibit COMT."	( Tolcapone in Parkinson's disease: liver toxicity and clinical efficacy. Borges, N, 2005)	0.33
" The acceptability of piribedil was assessed by physical examination, weight, blood pressure and heart rate as well as the reported adverse events."	( Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson's disease: a 6-month open study. Bundhukul, A; Chankrachang, S; Laptikultham, S; Nidhinandana, S; Pisarnpong, A; Srisuwananukorn, S; Suwantamee, J, 2004)	0.32
" Hoehn and Yahr stage and Schwab and England Activities of Daily Living Scale were also significantly improved Reported adverse events were mainly gastrointestinal symptoms."	( Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson's disease: a 6-month open study. Bundhukul, A; Chankrachang, S; Laptikultham, S; Nidhinandana, S; Pisarnpong, A; Srisuwananukorn, S; Suwantamee, J, 2004)	0.32
" Alterations of VMAT2 function might therefore cause cytoplasmic accumulation of free DA, which is toxic for dopaminergic neurons."	( Increased vulnerability to L-DOPA toxicity in dopaminergic neurons From VMAT2 heterozygote knockout mice. Hirano, M; Kariya, S; Takahashi, N; Ueno, S, 2005)	0.33
" Twenty-four drug-related adverse events were recorded of which four were regarded as serious."	( Efficacy and safety of high-dose cabergoline in Parkinson's disease. Ludolph, A; Odin, P; Oehlwein, C; Polzer, U; Renner, R; Schüler, P; Shing, M; Storch, A; Werner, G, 2006)	0.33
"The authors examined age effects on adverse events from two randomized, controlled trials of rasagiline, comparing younger (younger than 70 years) and older (70 years and older) subjects."	( Safety of rasagiline in elderly patients with Parkinson disease. Eberly, SW; Goetz, CG; Oakes, D; Schwid, SR; Shoulson, I, 2006)	0.33
" Outcome measures were overall improvement, quality of life, reduction of levodopa dose, and adverse events."	( Efficacy and safety of herbal medicines for idiopathic Parkinson's disease: a systematic review. Bian, Z; Chung, V; Gao, J; Kum, WF; Leuk Fong, W; Li, M; Liu, L; Zhao, Z, 2006)	0.56
"Although unilateral pallidotomy is generally considered a safe and effective neurosurgical treatment for advanced Parkinson's disease (PD), controversies concerning efficacy and adverse effects of bilateral posteroventral pallidotomy (PVP) exist and need to be resolved."	( Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson's disease. Chung, SJ; Hong, SH; Jeon, SR; Kim, SR; Lee, MC, 2006)	0.33
"Simultaneous bilateral PVP may be a safe and highly effective method of reducing levodopa-induced dyskinesia."	( Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson's disease. Chung, SJ; Hong, SH; Jeon, SR; Kim, SR; Lee, MC, 2006)	0.56
"Tolcapone seemed to be safe and was generally well tolerated as an adjunctive treatment in patients starting treatment with carbidopa/levodopa for symptomatic PD."	( Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson's disease. Lees, AJ; Oertel, WH; Ratziu, V; Tolosa, E, 2007)	0.54
" Meanwhile, recent studies have emphasized that genetic factors may involve in the occurrence of the adverse effects of chronic L-dopa therapy in PD patients."	( Genetic polymorphism of the angiotensin converting enzyme and L-dopa-induced adverse effects in Parkinson's disease. Harn, HJ; Lin, JJ; Lin, SZ; Liu, JT; Yueh, KC, 2007)	0.34
" Safety assessments included adverse events and oropharyngeal findings."	( Safety and efficacy of newly formulated selegiline orally disintegrating tablets as an adjunct to levodopa in the management of 'off' episodes in patients with Parkinson's disease. Bertoni, J; Kricorian, G; Leehey, M; Lew, MF; Pahwa, R, 2007)	0.56
" Treatment-related adverse events occurred in 132 (52%) patients."	( Safety and efficacy of newly formulated selegiline orally disintegrating tablets as an adjunct to levodopa in the management of 'off' episodes in patients with Parkinson's disease. Bertoni, J; Kricorian, G; Leehey, M; Lew, MF; Pahwa, R, 2007)	0.56
"Long-term treatment of L-dopa for Parkinson's disease (PD) patients induces adverse effects, including dyskinesia, on-off and wearing-off symptoms."	( The role of 3-O-methyldopa in the side effects of L-dopa. Charlton, C; Chen, H; King, J; Lee, ES, 2008)	0.35
" Among genetic factors, increasing evidences suggest that deletion/insertion (D/I) gene polymorphism of the angiotensin I-converting enzyme (ACE) may be involved in the pathogenesis of PD and in the occurrence of the adverse effects of chronic L-dopa therapy."	( Genetic polymorphism of Angiotensin-Converting Enzyme is not associated with the development of Parkinson's disease and of L-dopa-induced adverse effects. Guglielmi, R; Meco, G; Pascale, E; Passarelli, E; Passarelli, F; Purcaro, C; Vestri, AR, 2009)	0.35
" Moreover, we described all adverse events (early and late) and studied daily levodopa doses before and 6 months after treatment."	( [Continuous dopaminergic stimulation by Duodopa in advanced Parkinson's disease: Efficacy and safety]. Annic, A; Defebvre, L; Destée, A; Devos, D; Dujardin, K; Seguy, D, )	0.36
" Adverse events were due to PEG positioning for four patients, the equipment (pump, connection, inner tube) for all patients and levodopa for four patients."	( [Continuous dopaminergic stimulation by Duodopa in advanced Parkinson's disease: Efficacy and safety]. Annic, A; Defebvre, L; Destée, A; Devos, D; Dujardin, K; Seguy, D, )	0.34
" There were few severe adverse events."	( Patient profile, indications, efficacy and safety of duodenal levodopa infusion in advanced Parkinson's disease. Devos, D, 2009)	0.59
" MMMA was not toxic in the bacterial assay, indicating that its toxicity is not related to increased oxidative stress."	( Synthesis and in vitro cytotoxicity profile of the R-enantiomer of 3,4-dihydroxymethamphetamine (R-(-)-HHMA): comparison with related catecholamines. Blanco, M; Felim, A; Herrera, G; Largeron, M; Neudörffer, A; O'Connor, JE, 2010)	0.36
" The Cochrane Collaboration guidelines were followed and the following data were extracted from each study: identifier (title and bibliographical reference), classification of the quality of the evidence (Jadad criteria), type and design of the study, number of patients, patient demographics (average age, sex), Parkinson's disease stage (Hoehn and Yahr Scale), treatment (monotherapy or adjuvant to levodopa), drugs used (including dosage and duration), study objective (safety or tolerability), method of evaluation of results, randomization and blinding, and description of all the adverse events in all treatment groups."	( Tolerability and safety of ropinirole versus other dopamine agonists and levodopa in the treatment of Parkinson's disease: meta-analysis of randomized controlled trials. Kulisevsky, J; Pagonabarraga, J, 2010)	0.76
"In all the included studies, dopamine agonists, including ropinirole, exhibited a higher incidence of adverse events than placebo."	( Tolerability and safety of ropinirole versus other dopamine agonists and levodopa in the treatment of Parkinson's disease: meta-analysis of randomized controlled trials. Kulisevsky, J; Pagonabarraga, J, 2010)	0.59
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."	( Developing structure-activity relationships for the prediction of hepatotoxicity. Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010)	0.36
" We show that both Synphilin-1 and α-synuclein are toxic by themselves, but when co-expressed, they suppress their toxicity reciprocally."	( Synphilin suppresses α-synuclein neurotoxicity in a Parkinson's disease Drosophila model. Fonseca-Ornelas, L; Hernández-Vargas, R; López-González, I; Reynaud, E; Riesgo-Escovar, J; Zurita, M, 2011)	0.37
" Combination of α-lipoic acid efficiently halting deleterious toxic effects of L-dopa, revealed normalization of catalepsy score in addition to amelioration of neurochemical parameters and apparent preservation of striatal ultrastructure integrity, indicating benefit of both symptomatic and neuroprotective therapy."	( Intervention of mitochondrial dysfunction-oxidative stress-dependent apoptosis as a possible neuroprotective mechanism of α-lipoic acid against rotenone-induced parkinsonism and L-dopa toxicity. Abdin, AA; Sarhan, NI, 2011)	0.37
" However, their use is limited by actual and perceived adverse events (AE)."	( Apomorphine injections: predictors of initial common adverse events and long term tolerability. Ferrara, JM; Hunter, C; Mostile, G; Ondo, WG, 2012)	0.38
" These data identify a new class of therapeutic in Parkinson's disease and highlight the potential benefits of studying illicit drugs that in themselves would never be considered safe for long-term therapy."	( A novel MDMA analogue, UWA-101, that lacks psychoactivity and cytotoxicity, enhances L-DOPA benefit in parkinsonian primates. Brotchie, JM; Fox, SH; Gandy, MN; Gomez-Ramirez, J; Huot, P; Johnston, TH; Lee, J; Lewis, KD; Martin-Iverson, M; McIldowie, M; Millar, Z; Nash, JE; Piggott, MJ; Salomonczyk, D; Thiele, S; Wagg, K; Yong-Kee, CJ, 2012)	0.38
"9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5."	( Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial. Barone, P; Hasegawa, K; Hattori, N; Hauser, RA; Kagimura, T; Kuno, S; Mizuno, Y; Poewe, W; Rascol, O; Sarashina, A; Schapira, AH; Yamamoto, M, )	0.13
" Due to the nature of the data, it is not possible to give exact numbers for the frequency of adverse events."	( Duodopa® treatment for advanced Parkinson's disease: a review of efficacy and safety. Nyholm, D, 2012)	0.38
" Primary outcomes included adverse events (AEs) and extent of rotigotine exposure."	( The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson's disease. Boroojerdi, B; Giladi, N; Surmann, E, 2013)	0.39
" Safety evaluation included haematology, biochemistry, urinalysis parameters and adverse event monitoring."	( Efficacy and safety of standardized extract of Trigonella foenum-graecum L seeds as an adjuvant to L-Dopa in the management of patients with Parkinson's disease. Joshi, V; Mohan, V; Nathan, J; Panjwani, S; Thakurdesai, PA, 2014)	0.4
" The possible toxic action of striatal GLU (retrograde excitotoxicity) on these cells, and on other neurons which innervate the striatum and which also degenerate in Parkinson's disease (thalamostriatal cells of the intralaminar thalamic nuclei), is still practically unexplored."	( Striatal glutamate induces retrograde excitotoxicity and neuronal degeneration of intralaminar thalamic nuclei: their potential relevance for Parkinson's disease. Morales, I; Rodriguez, M; Sabate, M, 2013)	0.39
"3 % of the safety population) withdraw, due to adverse drug reaction (5), procedure and device related events (7), compliance (3) and lack of efficacy (8)."	( Effect and safety of duodenal levodopa infusion in advanced Parkinson's disease: a retrospective multicenter outcome assessment in patient routine care. Antonini, A; Bertaina, I; Calandrella, D; Cras, C; De Deyn, P; Gasser, UE; Mancini, F; Minafra, B; Odin, P; Opiano, L; Pacchetti, C; Pickut, B; Poewe, W; Spielberger, S; Tomantschger, V; Wolf, E; Zibetti, M, 2013)	0.68
" Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients."	( Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial. Ma, YZ; Shen, XM; Zhang, J, 2013)	0.39
" The Unified Parkinson's Disease Rating Scale scores, TCM symptoms scores, quality of life, change of Madopar's dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period."	( Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial. Ma, YZ; Shen, XM; Zhang, J, 2013)	0.39
" The most frequent adverse event experienced in the ropinirole PR group was dyskinesia."	( The efficacy and safety of ropinirole prolonged release tablets as adjunctive therapy in Chinese subjects with advanced Parkinson's disease: a multicenter, double-blind, randomized, placebo-controlled study. Cai, M; Cao, H; Chen, S; Cheng, Y; Li, J; Liu, C; Qu, Q; Wang, J; Wang, Z; Zhang, B; Zhang, X; Zhang, Z; Zhu, R, 2013)	0.39
" The adverse events observed were consistent with the established safety profile of ropinirole, with no new safety signal identified."	( The efficacy and safety of ropinirole prolonged release tablets as adjunctive therapy in Chinese subjects with advanced Parkinson's disease: a multicenter, double-blind, randomized, placebo-controlled study. Cai, M; Cao, H; Chen, S; Cheng, Y; Li, J; Liu, C; Qu, Q; Wang, J; Wang, Z; Zhang, B; Zhang, X; Zhang, Z; Zhu, R, 2013)	0.39
"Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations."	( Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients. Altmann, V; Callegari-Jacques, SM; Hutz, MH; Medeiros, MS; Monte, TL; Rieck, M; Rieder, CR; Schumacher-Schuh, AF; Tovo-Rodrigues, L, 2014)	2.09
"Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system."	( Toxicity and metabolism of layered double hydroxide intercalated with levodopa in a Parkinson's disease model. Ain, NM; Fakurazi, S; Hussein, MZ; Hussein-Al-Ali, SH; Kura, AU, 2014)	0.64
"The results suggest that compounds that indirectly facilitate 5-HT1 A receptor activation, such as citalopram, may be more effective therapeutics than direct 5-HT1 A receptor agonists because they exhibit similar anti-dyskinesia efficacy, while possessing a reduced side effect profile."	( Side effect profile of 5-HT treatments for Parkinson's disease and L-DOPA-induced dyskinesia in rats. Bishop, C; Conti, MM; Lindenbach, D; Ostock, CY; Palumbo, N; Vilceus, N, 2015)	0.42
" Outcome measures included improvement in motor functions; symptomatic improvement; improvement in quality of life; adverse effects."	( Safety and efficacy of rasagiline in addition to levodopa for the treatment of idiopathic Parkinson's disease: a meta-analysis of randomised controlled trials. Cai, B; Cai, JP; Chen, WJ; Lin, Y; Wang, N, 2015)	0.67
" There were no significant differences in adverse effects."	( Safety and efficacy of rasagiline in addition to levodopa for the treatment of idiopathic Parkinson's disease: a meta-analysis of randomised controlled trials. Cai, B; Cai, JP; Chen, WJ; Lin, Y; Wang, N, 2015)	0.67
"5 to 1 mg/day rasagiline in addition to levodopa is a safe and well-tolerated combination therapy for individuals with Parkinson's disease."	( Safety and efficacy of rasagiline in addition to levodopa for the treatment of idiopathic Parkinson's disease: a meta-analysis of randomised controlled trials. Cai, B; Cai, JP; Chen, WJ; Lin, Y; Wang, N, 2015)	0.94
" Continuous LCIG infusion tolerability and adverse drug reactions were consistent with the known safety profile of previous studies."	( Global long-term study on motor and non-motor symptoms and safety of levodopa-carbidopa intestinal gel in routine care of advanced Parkinson's disease patients; 12-month interim outcomes. Antonini, A; Bergmann, L; Poewe, W; Preda, C; Yegin, A, 2015)	0.65
" Safety assessments included monitoring adverse events (AEs), neurological examination, Gambling Symptom Assessment Scale questionnaire, liver chemistry, and laboratory tests."	( An open-label extension study to evaluate the safety of ropinirole prolonged release in Chinese patients with advanced Parkinson's disease. Cai, M; Chen, S; Cheng, Y; Hu, J; Li, J; Liu, C; Qu, Q; Wang, J; Wang, Z; Zhang, B; Zhang, X; Zhang, Z; Zhu, R, 2015)	0.42
" Most subjects (95%) reported ≥1 adverse event (AE); only 3 subjects (4."	( Long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal gel: an open-label extension of the double-blind pivotal study in advanced Parkinson's disease patients. Benesh, J; Chatamra, K; Dubow, J; Eaton, S; Fernandez, HH; Hall, C; Slevin, JT; Zadikoff, C, 2015)	0.67
"The objective of this study was to investigate the risk factors of wearing-off phenomenon in Parkinson's disease (PD) and propose safe dosage of levodopa to reduce wearing-off development based on Chinese cohort."	( Risk factors and safe dosage of levodopa for wearing-off phenomenon in Chinese patients with Parkinson's disease. Chen, H; Fang, J; Feng, T; Gao, L; Li, F, 2015)	0.9
" Adverse events of IPX066 from the different trials are presented."	( Safety of IPX066 , an extended release carbidopa-levodopa formulation, for the treatment of Parkinson's disease. Fahn, S; Kestenbaum, M, 2015)	0.67
" Pharmacokinetics, adverse events (AEs), and efficacy were assessed."	( Jejunal Infusion of levodopa-carbidopa intestinal gel versus oral administration of levodopa-carbidopa tablets in japanese subjects with advanced Parkinson's disease: pharmacokinetics and pilot efficacy and safety. Benesh, J; Chatamra, K; Dutta, S; Mohamed, ME; Nagai, M; Othman, AA; Yanagawa, M, 2015)	0.74
" Reported adverse events were comparable between LB and LC users."	( Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson's disease patients with wearing-off. Kuoppamäki, M; Leinonen, M; Poewe, W, 2015)	0.69
"Beyond the new generation non ergot dopamine agonists, no strong evidences allow the choice of a specific dopamine agonists for Parkinson 's disease treatment and by now dopamine agonists treatment should be tailored on specific adverse events profile."	( A review of adverse events linked to dopamine agonists in the treatment of Parkinson's disease. Bonuccelli, U; Ceravolo, R; Del Prete, E; Rossi, C, 2016)	0.43
"Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device-associated (n = 395) from non-procedure/device adverse events (n = 412)."	( Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials. Benesh, JA; Boyd, JT; Chatamra, K; Chouinard, S; Draganov, PV; Dubow, J; Eaton, S; Espay, AJ; Fasano, A; Fernandez, HH; Fung, VS; Klostermann, F; Lang, AE; Lew, MF; Odin, P; Robieson, WZ; Rodriguez, RL; Schmulewitz, N; Slevin, JT; Stein, DA; Zadikoff, C, 2016)	0.75
" Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively)."	( Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials. Benesh, JA; Boyd, JT; Chatamra, K; Chouinard, S; Draganov, PV; Dubow, J; Eaton, S; Espay, AJ; Fasano, A; Fernandez, HH; Fung, VS; Klostermann, F; Lang, AE; Lew, MF; Odin, P; Robieson, WZ; Rodriguez, RL; Schmulewitz, N; Slevin, JT; Stein, DA; Zadikoff, C, 2016)	0.75
" The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy."	( Drug-Induced Mitochondrial Toxicity. Al Shahrani, M; Hargreaves, IP; Heales, SJ; Wainwright, L, 2016)	0.43
" The issue of toxicity was raised in vitro studies, and suggests that L-dopa can be toxic to dopaminergic neurons, but it is not yet entirely proven."	( Protective effect of two essential oils isolated from Rosa damascena Mill. and Lavandula angustifolia Mill, and two classic antioxidants against L-dopa oxidative toxicity induced in healthy mice. Gadjeva, V; Karamalakova, Y; Kovacheva, N; Nikolova, G; Stanev, S; Zheleva, A, 2016)	0.43
" Adverse events caused the premature study discontinuation of 12 individuals (4."	( Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. Anand, R; Fox, SH; Hauser, RA; Jankovic, J; Jost, WH; Kenney, C; Kulisevsky, J; Pahwa, R; Poewe, W; Schapira, AH, 2017)	0.7
" The most frequently reported adverse event was dyskinesia (in 40 [14."	( Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. Anand, R; Fox, SH; Hauser, RA; Jankovic, J; Jost, WH; Kenney, C; Kulisevsky, J; Pahwa, R; Poewe, W; Schapira, AH, 2017)	0.7
" At higher doses, 50 mg/500 mg/125 mg SpinalonTM was considered to have reached maximum tolerated dose (MTD) since 3 out of 4 subjects experienced related adverse events including vomiting."	( Double-Blind, Placebo-Controlled, Randomized Phase I/IIa Study (Safety and Efficacy) with Buspirone/Levodopa/Carbidopa (SpinalonTM) in Subjects with Complete AIS A or Motor-Complete AIS B Spinal Cord Injury. Dyck, S; Guertin, PA; Kia, M; Matte, G; Mongeon, D; Prince, F; Radhakrishna, M; Roberts, M; Steuer, I; Vaillancourt, M, 2017)	0.67
" The primary outcome measure was safety assessed through adverse events (AEs)."	( ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson's Disease (EASE LID 2 Study): Interim Results of an Open-Label Safety Study. Felt, L; Hauser, RA; Isaacson, SH; Johnson, R; Oertel, W; Pahwa, R; Stempien, MJ; Tanner, CM, 2017)	0.71
" However, patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions."	( Efficacy and Safety of Adjuvant Treatment with Entacapone in Advanced Parkinson's Disease with Motor Fluctuation: A Systematic Meta-Analysis. Chen, J; Li, J; Liu, X; Lou, Z; Sun, Y, 2017)	0.46
"LCIG infusion is a safe and efficacious treatment for the control of motor fluctuations, and for improvement or nonworsening of nonmotor aspects, long-term sustained, and feasible for use in routine care."	( Long-term safety and effectiveness of levodopa-carbidopa intestinal gel infusion. Abu-Suboh, M; Alvarez-Sabín, J; Armengol, JR; De Fabregues, O; Dot, J; Ferré, A; Gómez, MR; Hernández-Vara, J; Ibarria, M; Puiggros, C; Quintana, M; Raguer, N; Romero, O; Seoane, JL, 2017)	0.73
" No systemic adverse effects were observed."	( Ninety-day Local Tolerability and Toxicity Study of ND0612, a Novel Formulation of Levodopa/Carbidopa, Administered by Subcutaneous Continuous Infusion in Minipigs. Manno, RA; Maronpot, RR; Nyska, A; Ramot, Y; Sacco, G; Shaltiel-Karyo, R; Tsarfati, Y; Yacoby-Zeevi, O, 2017)	0.68
" Assessments included spirometry and treatment-emergent adverse events (TEAEs)."	( Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease. Batycky, R; Corbin, A; LeWitt, PA; Murck, H; Pahwa, R; Sedkov, A, 2018)	0.74
" CVT-301 was generally safe and well tolerated."	( Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease. Batycky, R; Corbin, A; LeWitt, PA; Murck, H; Pahwa, R; Sedkov, A, 2018)	0.74
" The age of the patient impacts the effect and adverse events of anti-parkinsonian treatment."	( Efficacy and safety of rotigotine in elderly patients with Parkinson's disease in comparison with the non-elderly: a post hoc analysis of randomized, double-blind, placebo-controlled trials. Iwaki, H; Kondo, H; Nomoto, M; Sakurai, M, 2018)	0.48
" In the safety evaluation, it was found that acupuncture combined with Madopar was associated with significantly fewer adverse effects including gastrointestinal reactions (RR=0."	( Effectiveness and safety of acupuncture combined with Madopar for Parkinson's disease: a systematic review with meta-analysis. Chen, L; Chen, W; Dong, H; Geng, G; Li, T; Liu, H; Zhan, S; Zhang, Z, 2017)	0.46
" For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator."	( Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis. Gupta, S; Kell, S; Khanna, S; LeWitt, PA; Rubens, R; Verhagen Metman, L, )	0.35
"Multiple daily doses of PF-06669571 were safe and well tolerated with no notable safety concerns."	( A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, in Subjects with Idiopathic Parkinson's Disease. DeMartinis, N; Duvvuri, S; Gurrell, R; Sun, P, 2018)	0.48
"Objective We conducted a study to obtain information that could be used to provide Parkinson's disease (PD) patients with appropriate advice on safe driving."	( The Clinical Findings Useful for Driving Safety Advice for Parkinson's Disease Patients. Aiba, I; Ando, R; Aoki, M; Hasegawa, K; Iwaki, H; Nagai, M; Nakashima, K; Nishikawa, N; Nomoto, M; Tsuboi, Y; Tsujii, T; Yabe, H, 2018)	0.48
" The most common adverse reactions with amantadine are constipation, cardiovascular dysfunction including QT prolongation, orthostatic hypotension and edema, neuropsychiatric symptoms such as hallucinations, confusion and delirium, nausea and livedo reticularis."	( Efficacy and safety of amantadine for the treatment of L-DOPA-induced dyskinesia. Perez-Lloret, S; Rascol, O, 2018)	0.48
" Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event."	( Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson's disease. Benesh, J; Boyd, JT; Chatamra, K; Eaton, S; Espay, AJ; Facheris, MF; Fernandez, HH; Fung, VSC; Hall, C; Lew, MF; Robieson, WZ; Rodriguez, RL; Slevin, JT; Standaert, DG; Vanagunas, AD; Zadikoff, C, 2018)	0.76
" Although adverse event rates decreased over time, vigilance is required for device-related complications and adverse events."	( Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson's disease. Benesh, J; Boyd, JT; Chatamra, K; Eaton, S; Espay, AJ; Facheris, MF; Fernandez, HH; Fung, VSC; Hall, C; Lew, MF; Robieson, WZ; Rodriguez, RL; Slevin, JT; Standaert, DG; Vanagunas, AD; Zadikoff, C, 2018)	0.76
"The toxic effects of Ochratoxin A (OTA), a fungal secondary metabolite of the genera Aspergillus and Penicillium with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) a Parkinson inducing drug were investigated to evaluate the neurotoxic effects exerted by OTA."	( Restorative effect of l-Dopa treatment against Ochratoxin A induced neurotoxicity. Anand, T; Bhat, PV; Khanum, F; Mohan Manu, T, 2018)	0.48
" Treatment-emergent adverse events (TEAEs) occurred in 50."	( Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study. Hattori, N; Kato, M; Mochizuki, H; Nagai, M; Nishimura, A; Takahashi, R; Takeda, A; Takeda, S, 2018)	0.48
" In total, 300 adverse events were classified as related to safinamide in 132 patients (44."	( [Effectiveness and safety of safinamide as add-on to levodopa in patients with parkinson's disease: non-interventional study]. Bosse, D; Delf, M; Jost, WH; Kupsch, A; Mengs, J, 2018)	0.73
"We aimed to provide evidence that subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and safe treatment option for older patients with Parkinson's disease (PD)."	( Bilateral subthalamic deep brain stimulation is an effective and safe treatment option for the older patients with Parkinson's disease. Ahn, JH; Cho, JW; Cho, KR; Kim, M; Lee, JI; Park, JH; Park, S; Youn, J, 2018)	0.48
" Treatment-emergent adverse events (TEAEs) were mostly mild or moderate and occurred in 83."	( Long-term safety and efficacy of adjunctive rasagiline in levodopa-treated Japanese patients with Parkinson's disease. Hattori, N; Mochizuki, H; Nagai, M; Nakaya, R; Nishimura, A; Takahashi, R; Takeda, A; Takeda, S, 2019)	0.76
" Treatments were safe and well tolerated."	( Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial. Batycky, R; Fernandez, HH; Hauser, RA; Isaacson, SH; Lew, M; LeWitt, PA; Lopez-Manzanares, L; Oh, C; Pahwa, R; Pourcher, E; Rudzínska, M; Saint-Hilaire, M; Sedkov, A; Waters, C, 2019)	0.8
"CVT-301 can improve UPDRS motor scores of patients with Parkinson's disease during in-clinic off periods, with few severe or serious adverse events."	( Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial. Batycky, R; Fernandez, HH; Hauser, RA; Isaacson, SH; Lew, M; LeWitt, PA; Lopez-Manzanares, L; Oh, C; Pahwa, R; Pourcher, E; Rudzínska, M; Saint-Hilaire, M; Sedkov, A; Waters, C, 2019)	0.8
" Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events."	( Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson's disease. Dolžan, V; Flisar, D; Georgiev, D; Kojović, M; Kramberger, MG; Pirtošek, Z; Redenšek, S; Trošt, M, 2019)	0.51
" We did not find any associations between selected polymorphisms and motor adverse events."	( Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson's disease. Dolžan, V; Flisar, D; Georgiev, D; Kojović, M; Kramberger, MG; Pirtošek, Z; Redenšek, S; Trošt, M, 2019)	0.51
" Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment."	( Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson's disease. Dolžan, V; Flisar, D; Georgiev, D; Kojović, M; Kramberger, MG; Pirtošek, Z; Redenšek, S; Trošt, M, 2019)	0.51
" Serious adverse events were largely similar between groups."	( Safety and efficacy of co-careldopa as an add-on therapy to occupational and physical therapy in patients after stroke (DARS): a randomised, double-blind, placebo-controlled trial. Bhakta, BB; Cozens, A; Farrin, AJ; Ford, GA; Hartley, S; Holloway, I; Meads, D; Pearn, J; Ruddock, S; Sackley, CM; Saloniki, EC; Santorelli, G; Walker, MF, 2019)	0.51
" More patients in the levodopa monotherapy and LCIG polytherapy groups experienced treatment-related adverse drug reactions (ADRs) including dyskinesias and serious ADRs than did patients in the LCIG monotherapy group."	( Levodopa-Carbidopa Intestinal Gel Monotherapy: GLORIA Registry Demographics, Efficacy, and Safety. Antonini, A; Bergmann, L; Kukreja, P; Poewe, W; Robieson, WZ, 2019)	2.27
"3% of opicapone-treated patients reported treatment-emergent adverse events (TEAEs) versus 57."	( Safety Profile of Opicapone in the Management of Parkinson's Disease. Ferreira, JJ; Gama, H; Lees, A; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P, 2019)	0.51
"Long-term use of opicapone once-daily over 1-year at doses of 25 mg or 50 mg was generally safe and well tolerated, supporting its clinical usefulness in the management of PD motor fluctuations."	( Safety Profile of Opicapone in the Management of Parkinson's Disease. Ferreira, JJ; Gama, H; Lees, A; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P, 2019)	0.51
" However, adverse events (AEs) are frequent."	( Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study. Baille, G; Blaise, AS; Carrière, N; Defebvre, L; Devos, D; Dujardin, K; Grolez, G; Kreisler, A; Kyheng, M; Moreau, C; Mutez, E; Seguy, D, 2020)	0.85
" Adverse events were generally mild and transient and were mostly reported during the dose titration phase."	( A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia. Bergquist, F; Dizdar, N; Grigoriou, S; Hansson, F; Johansson, A; Nyholm, D; Odin, P; Rinne, J; Sonesson, C; Svenningsson, P; Tedroff, J; Tsitsi, P; Wictorin, K, 2020)	0.56
"IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia."	( A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia. Bergquist, F; Dizdar, N; Grigoriou, S; Hansson, F; Johansson, A; Nyholm, D; Odin, P; Rinne, J; Sonesson, C; Svenningsson, P; Tedroff, J; Tsitsi, P; Wictorin, K, 2020)	0.56
" Adverse events occurred in 58."	( Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study. Hattori, N; Nomoto, M; Sasagawa, Y; Tsuboi, Y; Yamamoto, A, 2020)	0.56
" Adverse events (AEs) occurred in 78."	( Long-term safety and efficacy of safinamide as add-on therapy in levodopa-treated Japanese patients with Parkinson's disease with wearing-off: Results of an open-label study. Hattori, N; Nomoto, M; Sasagawa, Y; Tsuboi, Y; Yamamoto, A, 2020)	0.8
"The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients."	( Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study. Caminiti, G; Casali, M; D'Antoni, V; Grassini, P; Stocchi, F; Tomino, C; Torti, M; Vacca, L; Volterrani, M, 2021)	0.62
" Other safety assessments included dyskinesia and adverse events (AEs)."	( A 12-month, dose-level blinded safety and efficacy study of levodopa inhalation powder (CVT-301, Inbrija) in patients with Parkinson's disease. Farbman, ES; Hauser, RA; Klingler, M; Lee, A; LeWitt, PA; Oh, C; Qian, J; Rudzińska, M; Waters, CH, 2020)	0.8
"Nilotinib was safe and tolerated, and no adverse effects seemed to be related to the drug, and no differences in adverse events were observed between groups."	( Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease. Ahn, J; Ferrante, D; Hebron, ML; Matar, S; Moussa, C; Mulki, S; Pagan, FL; Torres-Yaghi, Y; Wilmarth, B, 2021)	0.62
"This study provides evidence that nilotinib is safe and tolerated in Parkinson's disease."	( Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease. Ahn, J; Ferrante, D; Hebron, ML; Matar, S; Moussa, C; Mulki, S; Pagan, FL; Torres-Yaghi, Y; Wilmarth, B, 2021)	0.62
"We searched PubMed for studies on PD patients treated with tolcapone, documenting the following outcomes: liver enzyme, adverse events (AEs), daily Off-time, levodopa daily dose, unified Parkinson's disease rating scale (UPDRS) part-III, quality of life (QoL), and non-motor symptoms."	( Safety and efficacy of tolcapone in Parkinson's disease: systematic review. Artusi, CA; Fabbri, M; Imbalzano, G; Lopiano, L; Sarro, L, 2021)	0.82
" Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations."	( Long-term safety and efficacy of opicapone in Japanese Parkinson's patients with motor fluctuations. Hattori, N; Maeda, T; Nishimura, A; Nomoto, M; Takahashi, R; Takeda, A; Tsuboi, Y; Yoshida, K, 2021)	0.62
" Moreover, patients will be actively monitored with regard to the occurrence of side effects of evaluated therapies, as well as adverse events that may be related to insufficient platelet inhibition (no-reflow phenomenon assessed immediately after PCI, administration of GPIIb/IIIa inhibitors during PCI, acute stent thrombosis)."	( ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial. Adamski, P; Buszko, K; Gasior, M; Gorący, J; Kleinrok, A; Kosobucka, A; Kubica, A; Kubica, J; Lesiak, M; Nadolny, K; Navarese, E; Niezgoda, P; Wojakowski, W, 2021)	0.62
" Various LCIG procedure/device-associated adverse events (AEs) have been reported; however, reports on their treatment have been limited."	( The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study. Fujioka, S; Fukuchi, T; Furukawa, K; Furune, S; Ikeda, Y; Jin, X; Kato, M; Koike, T; Kubota, E; Murakami, H; Sato, Y; Suzuki, T; Tsuboi, Y; Uehara, T; Yamashita, K; Yamazaki, Y; Yube, Y, 2021)	0.62
" Therefore, the LCIG treatment is feasible and safe and is a unique treatment option for PD, requiring endoscopists' understanding and cooperation."	( The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study. Fujioka, S; Fukuchi, T; Furukawa, K; Furune, S; Ikeda, Y; Jin, X; Kato, M; Koike, T; Kubota, E; Murakami, H; Sato, Y; Suzuki, T; Tsuboi, Y; Uehara, T; Yamashita, K; Yamazaki, Y; Yube, Y, 2021)	0.62
"In summary, PIG-J insertion is safe with a similar complication rate to traditional PEG-J, well tolerated and effective for use in LCIG administration."	( Per-oral image guided gastrojejunostomy insertion for levodopa-carbidopa intestinal gel in Parkinson's disease is safe and may be advantageous. Baig, F; Boca, M; Cheminais, L; Collin, N; Mooney, L; Rolinski, M; Selikhova, M; Szewczyk-Krolikowski, K; Whone, A, 2021)	0.87
"Drugs affecting dopaminergic neurotransmission may exert toxic and beneficial effects that persist after discontinuation by modulating gene expression in key brain regions."	( Converging dopaminergic neurotoxicity mechanisms of antipsychotics, methamphetamine and levodopa. Dimitriou, A; Efthimiou, P; Karveli, M; Lagadinou, M; Skaltsa, M; Tsigkou, A; Velissaris, D; Zareifopoulos, N, 2021)	0.84
"The dopaminergic neurotoxins 6-oxidopamine and 1-methyl-4-phenyl-tetrahydropyridine (MPTP) promote oxidative stress and inhibit mitochondrial function, while their affinity for the dopamine transporter ensures they are attain toxic intracellular concentrations exclusively in dopaminergic neurons."	( Converging dopaminergic neurotoxicity mechanisms of antipsychotics, methamphetamine and levodopa. Dimitriou, A; Efthimiou, P; Karveli, M; Lagadinou, M; Skaltsa, M; Tsigkou, A; Velissaris, D; Zareifopoulos, N, 2021)	0.84
"Safinamide was well tolerated as a treatment for PD, and there was no significant difference in the frequency and severity of adverse events between the safinamide and placebo groups."	( Efficacy and safety evaluation of safinamide as an add-on treatment to levodopa for parkinson's disease. Fujioka, S; Kurihara, K; Mishima, T; Tsuboi, Y, 2022)	0.95
" The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events."	( Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis. Jiang, DQ; Jiang, LL; Li, MX; Lu, CS; Wang, Y, 2021)	0.86
" Pivotal secondary endpoints were changes in the sub-items of UDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, and adverse drug reactions (ADRs)."	( Efficacy and safety of istradefylline in patients with Parkinson's disease presenting with postural abnormalities: Results from a multicenter, prospective, and open-label exploratory study in Japan. Ito, H; Kajimoto, Y; Koh, J; Mori, A; Shimokawa, T; Takahashi, M; Takeshima, T; Yamashita, H, 2022)	0.72
" Eligible studies were synthesized for efficacy, tolerability, OFF time, Unified Parkinson's Disease Rating Scale part III score, ON state with dyskinesia, and the incidence of treatment-emergent adverse events."	( Efficacy and safety of istradefylline for Parkinson's disease: A systematic review and meta-analysis. Chen, B; Feng, ST; Hu, D; Wang, XL; Wang, ZZ; Zhang, Y, 2022)	0.72
" A total of 43 minor complications and 16 serious adverse events were reported."	( [Adverse effects and complications of continuous intestinal infusion of levodopa-carbidopa in a cohort of patients with Parkinson's disease in a tertiary hospital]. Baviera-Muñoz, R; Campins-Romeu, M; Losada-López, M; Martínez-Torres, I; Morata-Martínez, C; Pérez-García, J; Pons-Beltrán, V; Sastre-Bataller, I, 2022)	0.95
" Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA)."	( Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells. Chen, H; Chen, J; Chen, S; Li, Q; Liu, J; Lu, Y; Shao, F; Tang, M; Wu, W; Xu, Z; Yang, D; Zhai, L, 2022)	0.9
"We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL)."	( Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion. Antonini, A; Biundo, R; Calandrella, D; Carecchio, M; Carrer, T; Del Sorbo, F; Farinati, F; Garrì, F; Mainardi, M; Pezzoli, G; Pistonesi, F; Russo, FP; Sandre, M; Savarino, E; Soliveri, P; Weis, L; Zecchinelli, AL, 2022)	0.93
" However, it requires invasive percutaneous endoscopic gastrojejunostomy (PEG-J) and may be associated with serious adverse effects (AE)."	( Adverse effects of levodopa/carbidopa intrajejunal gel treatment: A single-center long-term follow-up study. Kramberger, MG; Križnar, NZ; Ocepek, L; Pirtošek, Z; Premzl, M; Rajnar, R; Rus, T; Trošt, M, 2022)	1.05
" The adverse drug reactions were those already described in the patients' information leaflet."	( Effectiveness and safety of safinamide in routine clinical practice in a Belgian Parkinson's disease population: an open-label, levodopa add-on study. Bergmans, B; Bourgeois, P; Cras, P; De Klippel, N; Dethy, S; Franco, G; Garraux, G; Geens, K; Jacquerye, P; Jeanjean, A; Krygier, C; Supiot, F; Van der Linden, C, 2023)	1.12
" Over this 4-week trial, and after a 4-month follow-up visit, levodopa/carbidopa treatment had no significant effect on ocular tolerability and anterior surface integrity, visual function, ocular health, refraction/ocular biometry, and did not induce any non-ocular adverse events."	( The safety and tolerability of levodopa eye drops for the treatment of ocular disorders: A randomized first-in-human study. Anstice, N; Ashby, R; Game, J; Jong, T; Karouta, C; Leung, M; Maddess, T; Morgan, IG; Sabeti, F; Thomson, K, 2022)	1.25
" Safety was evaluated through the frequency of adverse events and serious adverse events, physical examination, vital signs, 12-lead electrocardiograms, and laboratory exams."	( The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson's Disease with Motor Fluctuations. Cattaneo, C; Chen, S; Dong, X; Liu, C; Lu, Z; Pan, X; Shang, H; Sun, X; Tan, Y; Tao, E; Tian, Y; Wang, B; Wei, Q; Xu, P, 2022)	0.93
" There were no significant between-group differences for adverse events or serious adverse events."	( The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson's Disease with Motor Fluctuations. Cattaneo, C; Chen, S; Dong, X; Liu, C; Lu, Z; Pan, X; Shang, H; Sun, X; Tan, Y; Tao, E; Tian, Y; Wang, B; Wei, Q; Xu, P, 2022)	0.93
" Pramipexole ER ranked first in overall withdrawals, and rotigotine transdermal patch ranked first in the incidence of adverse events (≥1 AEs)."	( Efficacy and safety of non-ergot dopamine-receptor agonists as an adjunct to levodopa in advanced Parkinson's disease: A network meta-analysis. Chen, FF; Chen, XT; Wen, SY; Zhang, Q; Zhou, CQ, 2023)	1.14
" We collected demographic data, disease and treatment histories, and recorded adverse events and adverse drug reactions (ADRs)."	( Safety and effectiveness of istradefylline as add-on therapy to levodopa in patients with Parkinson's disease: Final report of a post-marketing surveillance study in Japan. Horiguchi, S; Ito, S; Takahashi, M; Tsuji, Y, 2022)	0.96
" Adverse events were reported in 63 (85%) of 74 patients in the foslevodopa-foscarbidopa group versus 42 (63%) of 67 in the levodopa-carbidopa group, and incidences of serious adverse events were similar between the groups (six [8%] of 74 vs four [6%] of 67, respectively)."	( Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Aldred, J; Budur, K; Facheris, MF; Fisseha, N; Fung, VS; Hauser, RA; Jeong, A; Kimber, TE; Klos, K; Litvan, I; O'Neill, D; Robieson, WZ; Soileau, MJ; Spindler, MA; Standaert, DG; Talapala, S; Vaou, EO; Zheng, H, 2022)	1.21
" For safety outcomes, rasagiline was associated with a higher incidence of adverse events than placebo and safinamide."	( Comparative efficacy and safety of monoamine oxidase type B inhibitors plus channel blockers and monoamine oxidase type B inhibitors as adjuvant therapy to levodopa in the treatment of Parkinson's disease: a network meta-analysis of randomized controlled Cai, G; Cai, H; Cui, Y; Feng, T; Lin, F; Su, D; Yan, R, 2023)	1.11
" Rasagiline is generally safe and well tolerated in Chinese PD patients."	( Safety and Effectiveness of Rasagiline in Chinese Patients with Parkinson's Disease: A Prospective, Multicenter, Non-interventional Post-marketing Study. Cao, S; Chen, H; Hu, X; Liang, Z; Liu, Z; Mao, W; Shao, M; Song, Z; Su, W; Tang, B; Wei, W; Wu, Y; Zhang, K, 2023)	0.91
" Only one medication has demonstrated improvement in dyskinesia in levodopa-treated PD patients; however, every patient cannot tolerate it and therefore adjunctive therapy should be tailored to an individual's symptoms and risk for specific adverse effects."	( Safety review of current pharmacotherapies for levodopa-treated patients with Parkinson's disease. Lyons, KE; Pahwa, R; Richmond, AM, )	0.62
" The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events."	( Systematic review of drug therapy for chorea in NXK2-1-related disorders: Efficacy and safety evidence from case studies and series. Bachoud-Lévi, AC; Blasco-Amaro, JA; Capuano, A; Isabel-Gómez, R; Martín-Gómez, C; Nou-Fontanet, L; Ortigoza-Escobar, JD; Zorzi, G, 2023)	0.91
" No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported."	( Systematic review of drug therapy for chorea in NXK2-1-related disorders: Efficacy and safety evidence from case studies and series. Bachoud-Lévi, AC; Blasco-Amaro, JA; Capuano, A; Isabel-Gómez, R; Martín-Gómez, C; Nou-Fontanet, L; Ortigoza-Escobar, JD; Zorzi, G, 2023)	1.16
" Unified Parkinson's Disease Rating Scale (UPDRS) total score and UPDRS part III score during on time were used to measure the overall severity of PD and motor complications, respectively, while the severity of adverse events was evaluated following the investigators' criteria."	( SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population. Avilés, A; Esquivel, A; Freire-Álvarez, E; Gómez-Esteban, JC; Kulisevsky, J; Legarda-Ramírez, I; Mata-Álvarez-Santullano, M, 2023)	0.91
" Increased safety concerns were undetected in any patient subgroup, although patients with cognitive impairment showed a slightly higher frequency of adverse events."	( SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population. Avilés, A; Esquivel, A; Freire-Álvarez, E; Gómez-Esteban, JC; Kulisevsky, J; Legarda-Ramírez, I; Mata-Álvarez-Santullano, M, 2023)	0.91
"This subanalysis further supports safinamide use as a safe and efficacious option for the management of motor fluctuations in different subgroups of levodopa-treated patients."	( SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population. Avilés, A; Esquivel, A; Freire-Álvarez, E; Gómez-Esteban, JC; Kulisevsky, J; Legarda-Ramírez, I; Mata-Álvarez-Santullano, M, 2023)	1.11
" Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD."	( Safety and feasibility of faecal microbiota transplantation for patients with Parkinson's disease: a protocol for a self-controlled interventional donor-FMT pilot study. Chernova, VO; Contarino, MF; Kuijper, EJ; Terveer, EM; van Hilten, JJ; Vendrik, KE, 2023)	0.91
" The adverse events described were mild, with generalised weakness, dizziness, nausea, headache and alopecia."	( Effectiveness and safety of safinamide in the Toledo Movement Disorders Unit. Diezma-Martín, A; García-Meléndez, DD; López-Ariztegui, N; Morales-Casado, MI, 2023)	0.91
"Safinamide has been shown to be effective and safe in improving motor fluctuations, motor symptoms and the subjective perception of disease severity in PD patients previously receiving rasagiline and in those receiving low-dose safinamide, all of which is accompanied by a good safety profile."	( Effectiveness and safety of safinamide in the Toledo Movement Disorders Unit. Diezma-Martín, A; García-Meléndez, DD; López-Ariztegui, N; Morales-Casado, MI, 2023)	0.91

Pharmacokinetics

Entacapone increased statistically significantly the mean area under the plasma concentration-time curve (AUC) of levodopa by 29% after a single dose and by 21% after 4 weeks' administration. Tolcapone increased the bioavailability (A UC 0-infinity) and apparent elimination half-life (t(1/2)) of levdopa by 80 and 40%, respectively, compared to placebo.

Excerpt	Reference	Relevance
" Thus, decarboxylase inhibition failed to alter the plasma half-life of levodopa."	( Levodopa pharmacokinetics. Alterations after benserazide, a decarboxylase inhibitor. Connor, JD; Doller, HJ; Dvorchik, BH; Lock, DR; Sloviter, RS; Vesell, ES, )	1.81
" This review summarises that available pharmacokinetic data involving levodopa, especially as it relates to therapeutic response of parkinsonian patients."	( Clinical pharmacokinetics of levodopa in parkinson's disease. Bianchine, JR; Shaw, GM, 1976)	0.78
" The plasma half-life clearance, volume of distribution, and maximum plasma concentrations of levodopa did not differ among groups."	( Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon. Carter, JH; Gancher, ST; Nutt, JG; Woodward, WR, 1992)	0.75
") pharmacokinetic profile of two controlled-release products of levodopa (Madopar HBS and Sinemet CR) was compared to conventional Madopar capsules in 18 healthy volunteers in a cross-over, randomized design."	( Comparative multiple-dose pharmacokinetics of controlled-release levodopa products. Collin, C; Eckernäs, SA; Grahnén, A; Ling-Andersson, A; Nilsson, M; Tiger, G, 1992)	0.76
" Most management problems are related to the pharmacokinetic and pharmacodynamic properties of levodopa."	( Pharmacokinetics and pharmacodynamics of levodopa. Montgomery, EB, 1992)	0.77
" administration of L-dopa, but had no effect on the half-life (t1/2) for its distribution or elimination."	( Peripheral pharmacokinetic handling and metabolism of L-dopa in the rat: the effect of route of administration and carbidopa pretreatment. Jenner, P; Marsden, CD; Rose, S, 1991)	0.28
" The pharmacokinetic and clinical data of these patients were compared retrospectively with those of Parkinsonian patients with fluctuations in motor performance but with preserved clinical responses to single oral doses of levodopa."	( Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa. Deleu, D; Ebinger, G; Michotte, Y, 1991)	0.7
"We address, from a pharmacokinetic viewpoint, the important question of why some patients with clinical idiopathic Parkinson's disease experience a fall off in benefit from levodopa maintenance therapy."	( Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease. Bowes, SG; Deshmukh, AA; Dobbs, RJ; Dobbs, SM; Leeman, AL; Nicholson, PW; O'Neill, CJ, 1991)	0.79
"kg-1) and a longer plasma elimination half-life (67."	( Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease. Albani, F; Baruzzi, A; Contin, M; Martinelli, P; Riva, R, 1991)	0.54
" After training, only a limited number of these models, could explain the pharmacodynamic data observed by Mouradian et al."	( A computational model of levodopa pharmacodynamics in Parkinson's disease. Jamieson, PW, 1991)	0.58
" For comparison, the pharmacokinetic parameters of both compounds were simultaneously determined in plasma using blood collection."	( In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle. A microdialysis study. Deleu, D; Ebinger, G; Michotte, Y; Sarre, S, 1991)	0.58
" route, elimination followed apparent first order kinetics and was biphasic with a t 1/2 alpha of 7 min and terminal half-life of 67 min."	( Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary excretion of gamma-L-glutamyl-L-dopa in the rat. Cummings, J; Matheson, LM; Maurice, L; Smyth, JF, 1990)	0.28
" These data suggest that pulsatile levodopa administration does not acutely alter dopamine receptor responsiveness, and that other pharmacokinetic and pharmacodynamic factors contribute to the dose-to-dose variability in response to levodopa."	( Acute effects of pulsatile levodopa administration on central dopamine pharmacodynamics. Baronti, F; Brughitta, G; Davis, TL; Mouradian, MM, 1991)	0.86
"Five patients with severe Parkinson's disease were characterized with respect to their pharmacokinetic and pharmacodynamic responses to levodopa given: orally, intravenously (three different infusion rates) and intraduodenally."	( Pharmacokinetics and effects of levodopa in advanced Parkinson's disease. Aquilonius, SM; Bredberg, E; Paalzow, L; Tedroff, J, 1990)	0.77
"" Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs."	( L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease. Cedarbaum, JM; Clark, M; Harts, A; Kutt, H; Silvestri, M, 1990)	0.89
" Dyskinesias may be considered a secondary pharmacodynamic consequence of such pharmacokinetically induced oscillations in brain dopamine levels."	( Pharmacokinetic and pharmacodynamic considerations in management of motor response fluctuations in Parkinson's disease. Cedarbaum, JM, 1990)	0.28
"Eight parkinsonian patients participated in a pharmacokinetic pharmacodynamic study of sequential doses of controlled-release carbidopa (CD)/levodopa (LD) at 4-hour intervals, with serial blood samples obtained before and after each dose."	( Pharmacodynamic modeling of concentration-effect relationships after controlled-release carbidopa/levodopa (Sinemet CR4) in Parkinson's disease. Berchou, RC; Galloway, MP; Kareti, D; LeWitt, PA; Nelson, MV, 1990)	0.7
" The disappearance of L-dopa from plasma and cisternal CSF compartments fits an open, two-compartment pharmacokinetic model."	( L-dopa pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys. Boucher, B; Gliessman, P; Hammerstad, JP; Nutt, JG; Woodward, WR, 1990)	0.28
"To assess the relative influence of central pharmacodynamic and peripheral pharmacokinetic factors on the duration of motor response to levodopa, the relationship between motor function and plasma levodopa levels was studied in 31 Parkinsonian patients."	( Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease. Bovingdon, M; Frankel, JP; Kempster, PA; Lees, AJ; Stern, GM; Webster, R, 1989)	1.92
" Delayed onset of antiparkinsonian effect of CR-4, resulting from an increase of Tmax for levodopa, was one of the major complaints and required additional small amounts of standard levodopa in three patients."	( Clinical and pharmacokinetic evaluation of controlled-release levodopa/carbidopa (CR-4) in parkinsonian patients with severe motor fluctuations: a six month follow-up study. Deleu, D; Ebinger, G; Jacques, M; Michotte, Y, 1989)	0.74
"Seventeen patients with advanced Parkinson's disease who had fluctuations in motor performance while taking standard Sinemet (STD) 25/100 underwent daylong pharmacokinetic and clinical observation studies while taking both STD and Sinemet CR, a new controlled-release formulation containing 50 mg carbidopa and 200 mg levodopa."	( A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100). Cedarbaum, JM; Kutt, H; McDowell, FH, 1989)	0.45
" Several hypotheses have explained the advantage of the combined treatment by a pharmacodynamic interaction in the striatum."	( The influence of levodopa in the pharmacokinetics of bromocriptine in Parkinson's disease. Bar, M; Graff, E; Isakov, A; Oberman, Z; Rabey, JM; Scharf, M, 1989)	0.62
" These observations were consistent with the pharmacokinetic characteristics of the formulation."	( Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. August, TF; Bush, DF; Lasseter, KC; Musson, DG; Schwartz, S; Smith, ME; Titus, DC; Yeh, KC, 1989)	0.28
" With pharmacokinetic studies correlated to clinical ratings, plasma levodopa was less variable during Sinemet CR treatment, and clinical responses showed greater uniformity."	( Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. Berchou, RC; Galloway, MP; Kareti, D; Kesaree, N; LeWitt, PA; Nelson, MV; Schlick, P, 1989)	0.8
" Delayed onset of antiparkinsonian effect of CR, resulting from an increase of Tmax for levodopa, was one of the major patient complaints and required additional small amounts of standard levodopa in some patients."	( Controlled-release carbidopa/levodopa (CR) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations. Deleu, D; Ebinger, G; Jacques, M; Michotte, Y, 1989)	0.79
" Mean L-DOPA plasma concentrations were fitted to a one-compartment pharmacokinetic model."	( Pharmacokinetic and pharmacodynamic modeling of L-dopa plasma concentrations and clinical effects in Parkinson's disease after Sinemet. Berchou, RC; Galloway, MP; Kareti, D; Kesaree, N; Lewitt, PA; Nelson, MV; Schlick, P, 1989)	0.28
" In 11 of 15 subjects, the disappearance of drug could be described by a two-compartment model, with a distribution half-life of 5 minutes and an elimination half-life of 33 minutes."	( Peripheral pharmacokinetics of apomorphine in humans. Boucher, B; Gancher, ST; Nutt, JG; Woodward, WR, 1989)	0.28
" This, in turn, is influenced by the fluctuating plasma concentrations of levodopa produced by the drug's short half-life and erratic absorption, and by modifiable transport at the blood-brain barrier."	( On-off phenomenon: relation to levodopa pharmacokinetics and pharmacodynamics. Nutt, JG, 1987)	0.79
"The principal peripheral pharmacokinetic parameters of the levodopa/carbidopa association were investigated in 11 healthy volunteers and in 16 patients at various stages of Parkinson disease, with and without the on-off phenomenon."	( Peripheral pharmacokinetic parameters of levodopa/carbidopa and the on-off phenomenon in parkinsonian patients. Bergamasco, B; Chiadò, I; De Gennaro, T; Delsedime, M; Gilli, M; Rainero, I; Riccio, A, 1988)	0.78
"The contribution of the peripheral and central pharmacokinetic mechanisms of levodopa to the pathogenesis of the motor fluctuations that complicate its long-term administration was studied in 28 parkinsonian patients."	( Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease. Chase, TN; Fabbrini, G; Juncos, J; Mouradian, MM; Serrati, C, 1987)	1.94
" There was no evidence of idiosyncratic pharmacokinetic or pharmacodynamic responses to levodopa to explain the fluctuating response."	( Levodopa pharmacokinetics and pharmacodynamics in fluctuating parkinsonian patients. Nutt, JG; Woodward, WR, 1986)	1.94
" 163) on the serum t1/2 and other pharmacokinetic parameters of co-administered L-3,4-dihydroxyphenylalanine (L-DOPA) were compared to those of the reversible inhibitor, carbidopa in rats."	( A comparison of the effects of reversible and irreversible inhibitors of aromatic L-amino acid decarboxylase on the half-life and other pharmacokinetic parameters of oral L-3,4-dihydroxyphenylalanine. Haegele, KD; Huebert, ND; Palfreyman, MG, )	0.13
"The relationship between the dose of levodopa and its pharmacokinetic behavior following intravenous and oral administration was investigated in dogs and parkinsonian patients."	( Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on pharmacokinetic behavior of levodopa in dogs and Parkinsonian patients. Habara, T; Morioka, T; Nakajima, E; Nitanai, T; Sasahara, K, 1980)	0.78
" Also, despite the differences in dose, the values of the Cmax were similar, with average values of 12."	( Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: a study of five different suppositories. Danhof, M; Jansen, EN; Neef, C; Roos, RA; van Laar, T, 1995)	0.29
" The dopamine concentration in the striatum increased immediately after L-dopa injection, with the peak concentration (15."	( Pharmacokinetic and pharmacodynamic studies of L-dopa in rats. II. Effect of L-dopa on dopamine and dopamine metabolite concentration in rat striatum. Koitabashi, T; Koshiro, A; Sato, S, 1994)	0.29
" Pretreatment with carbidopa had no significant effect on the pharmacokinetic parameters of L-dopa in blood plasma, but resulted in an increase in the area under the concentration versus time curve (AUC) and elimination half-life (t1/2) of L-dopa in muscle ECF (0."	( The effect of carbidopa and entacapone pretreatment on the L-dopa pharmacokinetics and metabolism in blood plasma and skeletal muscle in beagle dog: an in vivo microdialysis study. Deleu, D; Ebinger, G; Michotte, Y; Sarre, S, 1995)	0.29
" The present study, therefore, compared single dose kinetics and pharmacodynamic effects of three dosages of L-dopa/bensearazid-s."	( [Slow-release L-dopa vs. standard L-dopa in Parkinson patients in various stages of the disease. Studies of pharmacokinetics and motor effectiveness]. Baas, H; Bergemann, N; Fischer, PA, 1994)	0.29
" The pharmacokinetic variables were then compared in both tissues with noncompartmental modeling."	( Simultaneous in vivo microdialysis in plasma and skeletal muscle: a study of the pharmacokinetic properties of levodopa by noncompartmental analysis. Deleu, D; Ebinger, G; Michotte, Y; Sarre, S, 1994)	0.5
" We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa."	( Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Beckner, RM; Berggren, K; Carter, JH; Gancher, ST; Gordin, A; Hammerstad, JP; Nutt, JG; Stone, CK; Woodward, WR, 1994)	0.72
" Conversely, levodopa equilibration half-life between plasma and effect-site concentration was five-fold shorter on average in fluctuating patients."	( Pharmacodynamic modeling of oral levodopa: clinical application in Parkinson's disease. Albani, F; Baruzzi, A; Contin, M; Cortelli, P; Martinelli, P; Riva, R, 1993)	0.94
" Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations."	( The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Gordin, A; Harjola, VP; Karlsson, M; Keränen, T; Korpela, K; Pentikäinen, PJ; Rita, H; Seppälä, L; Wikberg, T, 1993)	0.8
" Tolcapone increased the area under the concentration-time curve and elimination half-life of levodopa."	( Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa. Da Prada, M; Dingemanse, J; Jorga, K; Schmitt, M; Sedek, G; Van Brummelen, P; Zürcher, G, 1995)	0.73
" Plasma levodopa and levodopa metabolite pharmacokinetic profiles were determined using standard techniques."	( A clinical and pharmacokinetic case study of an interaction of levodopa and antituberculous therapy in Parkinson's disease. O'Connell, MT; Patsalos, PN; Quinn, NP; Wenning, GK, 1995)	0.97
" The mean plasma concentration-time curves on each occasion were essentially superimposable and there were no significant differences in any calculated pharmacokinetic parameter."	( The effect of selegiline on the peripheral pharmacokinetics of levodopa in young volunteers. Macklin, BS; O'Shea, N; Renwick, AG; Roberts, J; Waller, DG, 1995)	0.53
" Plasma concentrations of levodopa, 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), carbidopa, and entacapone were determined for pharmacokinetic calculations."	( Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa-carbidopa in volunteers. Ahtila, S; Gordin, A; Heinävaara, S; Kaakkola, S; Karlsson, M; Korpela, K; Männistö, PT; Tuomainen, P; Wikberg, T, 1995)	0.82
" Entacapone increased statistically significantly the mean area under the plasma concentration-time curve (AUC) of levodopa by 29% after a single dose and by 21% after 4 weeks' administration, without affecting other pharmacokinetic parameters of levodopa."	( Effect of one month's treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Rinne, UK; Ruottinen, HM, 1996)	0.7
"A pharmacokinetic model of oral levodopa is proposed to elucidate the effects of carbidopa on the pharmacokinetics of levodopa."	( Pharmacokinetic model of oral levodopa and role of carbidopa in parkinsonian patients. Hasegawa, T; Mizutani, Y; Nabeshima, T; Ogawa, M; Okada, Y, 1995)	0.86
" The levodopa plasma half-life is very short, resulting in marked plasma drug concentration fluctuations which are matched, as the disease progresses, with swings in the therapeutic response ('wearing-off' phenomena)."	( Pharmacokinetic optimisation in the treatment of Parkinson's disease. Albani, F; Baruzzi, A; Contin, M; Riva, R, 1996)	0.81
"We compared the pharmacokinetic and motor responses of Sinemet and Atamet (generic carbidopa/levodopa) in patients with Parkinson's disease."	( Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a single-dose study. Koller, WC; Lyons, K; Marjama, J; McGuire, D; Pahwa, R; Silverstein, P; Ward, R; Zwiebel, F, 1996)	0.75
" Most of these data to levodopa pharmacodynamics can be explained by a model which is presented in this paper and which is mainly based on cerebral pharmacokinetic mechanisms."	( Fluctuations in Parkinson's disease. Pathogenetic significance of levodopa's cerebral pharmacokinetics and pharmacodynamics. Baas, H; Bürklin, F; Demisch, L; Fischer, PA; Harder, S; Stecker, K, 1995)	0.84
" A moment analysis was also made to obtain pharmacokinetic parameters."	( In vivo microdialysis to determine the relative pharmacokinetics of drugs. Ichikawa, M; Matsuyama, K; Nakashima, M; Nakashima, MN; Sakurai, M; Sasaki, H; Zhao, MF, 1996)	0.29
" A temporal variation of the kinetics of both L-dopa and carbidopa was demonstrated with higher plasma clearance and lower area under concentration curve after the administration at 2200 hours."	( Circadian phase dependent pharmacokinetics of L-dopa, its main metabolites (3-OMD, HVA, DOPAC) and carbidopa in rats. Andre, MH; Bruguerolle, B; Grignon, S, 1996)	0.29
" Levodopa plasma concentration data and motor effect behaviour (tapping times) were obtained from 46 patients, for whom a total of 970 observations were available (approximately 21 pharmacokinetic and pharmacodynamic observations per patient)."	( Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian patients. Albani, F; Baruzzi, A; Charles, BG; Contin, M; Cortelli, P; Martinelli, P; Riva, R; Triggs, EJ, 1996)	1.45
"In the final regression models the Hoehn and Yahr (HY) status of the patient and duration of disease (DUR) were found to be important determinants of the pharmacodynamic parameters for levodopa."	( Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian patients. Albani, F; Baruzzi, A; Charles, BG; Contin, M; Cortelli, P; Martinelli, P; Riva, R; Triggs, EJ, 1996)	0.73
"In a clinical setting knowledge of the population pharmacokinetic and pharmacodynamic parameters for oral levodopa may prove useful in estimating the duration of the drug's beneficial motor activity in patients with mild to severe Parkinson's disease (Hoehn and Yahr status I-IV)."	( Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian patients. Albani, F; Baruzzi, A; Charles, BG; Contin, M; Cortelli, P; Martinelli, P; Riva, R; Triggs, EJ, 1996)	0.75
" Tolcapone had similar effects on plasma levodopa concentrations with the standard-release formulations: half-life and bioavailability increased approximately 2-fold compared with placebo, and maximum plasma concentration (Cmax) and time to Cmax (tmax) were unaffected, except for a slight increase in Cmax with the levodopa/benserazide 200/ 50 mg formulation."	( The effect of COMT inhibition by tolcapone on tolerability and pharmacokinetics of different levodopa/benserazide formulations. Aitken, J; Fotteler, B; Jorga, K; Nielsen, T; Schmitt, M; Zürcher, G, 1997)	0.78
" As predicted from the plasma half-life (1."	( Controlled release levodopa/carbidopa 25/100 (Sinemet CR 25/100): pharmacokinetics and clinical efficacy in untreated parkinsonian patients. Block, GA; Cyhan, G; Gancher, ST; Hammerstad, JP; Nutt, JG; Woodward, WR, 1994)	0.62
"Previous investigations on the mutual pharmacokinetic influence of L-dopa and dopamine agonists in Parkinson's disease (PD) have shown controversial results."	( Clinical and pharmacokinetic evaluation of L-dopa and cabergoline cotreatment in Parkinson's disease. Bonuccelli, U; Colzi, A; Del Dotto, P; Fariello, R; Musatti, E; Persiani, S; Strolin Benedetti, M, 1997)	0.3
" Nevertheless, the pharmacokinetic profile of the preparation has a number of advantages over that of Sinemet, in that it offers a steadier climb to peak plasma concentrations that are less extreme and of greater duration."	( Pharmacokinetics of continuous-release carbidopa/levodopa. Mark, MH; Sage, JI, 1994)	0.54
" All patients underwent 10-h pharmacokinetic and clinical evaluations while on Std-L and again while on L-CR."	( Comparison of standard carbidopa-levodopa and sustained-release carbidopa-levodopa in Parkinson's disease: pharmacokinetic and quality-of-life measures. Koller, WC; Lyons, K; McGuire, D; Pahwa, R; Robischon, M; Silverstein, P; Zwiebel, F, 1997)	0.58
" The peak levodopa concentration (Cmax) and the area under the time-concentration curve (AUC) were markedly increased after long-term levodopa therapy, whereas the time to the peak concentration (Tmax) and the elimination half-life (T(1/2)) were decreased."	( Effects of chronic levodopa therapy on dopa pharmacokinetics. Kanazawa, I; Murata, M, 1997)	1.03
" It has an appropriate receptor affinity profile, with potent and long-lasting dopaminergic stimulatory effects in 6-hydroxydopamine-lesioned rats and in MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine)-lesioned primates; it has a consistent pharmacokinetic profile, with a very long mean plasma elimination half-life of 65 to 110 hours, and its absorption and excretion are unaffected by food, age or renal or hepatic disease; moreover, when given concomitantly, cabergoline does not influence levodopa pharmacokinetics."	( Pharmacodynamic and pharmacokinetic features of cabergoline. Rationale for use in Parkinson's disease. Fariello, RG, 1998)	0.46
"The modification of the pharmacodynamic response to a single oral dose of levodopa/benserazide by the coadministration of the dopamine agonist apomorphine was investigated in parkinsonian patients with end-of-dose motor fluctuations."	( Pharmacodynamics of levodopa coadministered with apomorphine in parkinsonian patients with end-of-dose motor fluctuations. Baas, H; Bürklin, F; Demisch, L; Fischer, PA; Harder, S, )	0.69
"Clinical pharmacology studies have shown that the catechol-O-methyltransferase inhibitor tolcapone increases the bioavailability area under the plasma concentration-time curve (AUC) and the plasma elimination half-life (t1/2) of levodopa."	( The effect of tolcapone on levodopa pharmacokinetics is independent of levodopa/carbidopa formulation. Aitken, J; Fotteler, B; Jorga, K; Nielsen, T; Sedek, G, 1998)	0.78
" When given together with levodopa/DCI, tolcapone increases the relative bioavailability and plasma elimination half-life of levodopa, without affecting its peak plasma concentration."	( Pharmacokinetics, pharmacodynamics, and tolerability of tolcapone: a review of early studies in volunteers. Jorga, KM, 1998)	0.6
" Blood samples were withdrawn for pharmacokinetic analysis, and the clinical response was measured using the motor part of the Unified Parkinson's Disease Rating Scale."	( Population pharmacodynamic modeling of levodopa in patients with Parkinson's disease receiving entacapone. Gordin, A; Karlsson, MO; Naukkarinen, TH; Rinne, UK; Ruottinen, HM; Trocóniz, IF, 1998)	0.57
"A population pharmacodynamic model for levodopa was built that took into account interindividual and intraindividual variability."	( Population pharmacodynamic modeling of levodopa in patients with Parkinson's disease receiving entacapone. Gordin, A; Karlsson, MO; Naukkarinen, TH; Rinne, UK; Ruottinen, HM; Trocóniz, IF, 1998)	0.84
"A multiple-dose study was performed to assess the pharmacokinetic profile of a new levodopa/benserazide dual-release formulation (DRF) in comparison with a conventional slow-release formulation (SRF)."	( Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy subjects. Crevoisier, C; Dingemanse, J; Gasser, UE; Lankhaar, G; Ouwerkerk, M, 1998)	0.77
"Thirty patients with Parkinson's disease not previously treated with dopamine agonists, of whom 28 produced evaluable pharmacokinetic data for ropinirole and 23 for L-dopa."	( Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with Parkinson's disease. Beerahee, A; Burns, E; Citerone, DR; Cyronak, MJ; Fitzpatrick, KL; Leigh, TJ; Lennox, G; Lopez-Gil, A; Taylor, AC; Vakil, SD, 1999)	0.3
"Primary end points were AUC0-8 and Cmax for ropinirole, and AUC0-8, AUC0-infinity and Cmax for L-dopa."	( Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with Parkinson's disease. Beerahee, A; Burns, E; Citerone, DR; Cyronak, MJ; Fitzpatrick, KL; Leigh, TJ; Lennox, G; Lopez-Gil, A; Taylor, AC; Vakil, SD, 1999)	0.3
"There are no pharmacokinetic grounds for adjusting dosages of either ropinirole or L-dopa when given in combination."	( Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with Parkinson's disease. Beerahee, A; Burns, E; Citerone, DR; Cyronak, MJ; Fitzpatrick, KL; Leigh, TJ; Lennox, G; Lopez-Gil, A; Taylor, AC; Vakil, SD, 1999)	0.3
" This clinical and pharmacokinetic study was repeated after 6 weeks of tolcapone therapy (200 mg three times daily)."	( Pharmacokinetics and pharmacodynamics of L-Dopa after acute and 6-week tolcapone administration in patients with Parkinson's disease. Bellini, G; Bonuccelli, U; Del Dotto, P; Dell'Agnello, G; Gambaccini, G; Napolitano, A; Petrozzi, L, )	0.13
" The advantage of the Dixon equation over the sigmoid equation is that the Dixon equation can take 3OMD into consideration for pharmacodynamic modelling."	( Pharmacodynamic modelling of levodopa, 3-O-methyldopa and their effects: an application of the Dixon equation. Furlanut, M; Wu, G, 1999)	0.59
" Tolcapone increased the bioavailability (AUC 0-infinity) and apparent elimination half-life (t(1/2)) of levodopa by 80 and 40%, respectively, compared to placebo."	( COMT inhibition by tolcapone further improves levodopa pharmacokinetics when combined with a dual-release formulation of levodopa/benserazide. A novel principle in the treatment of Parkinson's disease. Crevoisier, C; Gasser, UE; Hovens, SE; Jorga, K; van Giersbergen, PL, 1999)	0.78
" Pharmacokinetic parameters calculated from plasma drug concentrations on days 1-2 and 6-7 were compared with each other."	( Pharmacokinetics of oral entacapone after frequent multiple dosing and effects on levodopa disposition. Gordin, A; Huhtala, S; Huupponen, R; Korpela, K; Reinikainen, K; Rouru, J; Savontaus, E; Scheinin, M, 1999)	0.53
"No changes in any pharmacokinetic parameters of carbidopa were observed."	( COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients in levodopa/carbidopa (Sinemet). Jorga, KM; Nicholl, DJ, 1999)	0.52
" The elimination half-life is very short (30 to 90 min) depending on the type of parenteral administration."	( Pharmacokinetic-pharmacodynamic relationships of apomorphine in patients with Parkinson's disease. Neef, C; van Laar, T, 1999)	0.3
"The pharmacokinetic model which best described the data was a two-compartment open model with first-order absorption and possibly a lag-time."	( Population pharmacokinetics of tolcapone in parkinsonian patients in dose finding studies. Banken, L; Fotteler, B; Jorga, K; Snell, P; Steimer, JL, 2000)	0.31
" The parameter estimates obtained agreed with those obtained from conventional pharmacokinetic studies and no subpopulation was shown to be at risk of either under- or over-exposure to tolcapone."	( Population pharmacokinetics of tolcapone in parkinsonian patients in dose finding studies. Banken, L; Fotteler, B; Jorga, K; Snell, P; Steimer, JL, 2000)	0.31
" Both agents extend the elimination half-life and plasma area under the curve of levodopa without affecting the maximal plasma concentration of levodopa (Cmax) or the time until an oral dose of levodopa reaches its peak plasma concentration (Tmax)."	( Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Nutt, JG, 2000)	0.76
"To understand the delay in the clinical benefit that commonly occurs after initiation of levodopa (L-Dopa) treatment, we examined the pharmacokinetic profile of L-Dopa after the first oral dose ever taken of L-Dopa/carbidopa in untreated patients with Parkinson's disease and followed these parameters after 1 month of treatment."	( The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo patients with Parkinson's disease. Djaldetti, R; Melamed, E; Rosmarin, V; Ziv, I, )	0.59
" Thereafter 6-[18F]levodopa PET was performed, and the influx rate constants (k(c)) for the putamen and the caudatus region were correlated with the median effective concentration (EC(50)) and the equilibrium half-life (T(eq)) of the PK-PD model."	( Levodopa pharmacokinetic-pharmacodynamic modeling and 6-[18F]levodopa positron emission tomography in patients with Parkinson's disease. Baas, H; Dietz, M; Graff, J; Harder, S; Künig, G; Leenders, KL; Vontobel, P, 2001)	2.08
" This effect was small but statistically significant for the area under the plasma concentration-time curve, whereas tmax (time of maximum plasma concentration) and peak-to-trough fluctuation were not affected."	( Influence of the dopamine agonist alpha-dihydroergocryptine on the pharmacokinetics of levodopa in patients with Parkinson's disease. Althaus, M; de Mey, C; Falup-Pecurariu, C; Minea, D; Retzow, A; Varga, I, )	0.35
"This study assessed the behavioural and pharmacokinetic effects of chronic oral administration of L-dopa plus carbidopa alone, or with co-administration of the peripheral COMT inhibitor entacapone, to normal macaque monkeys."	( L-dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic observations. Heikkilä, M; Jenner, P; Lindén, IB; Pearce, RK, 2001)	0.31
" The present study describes the pharmacokinetic properties of (S)-UH-301 after subcutaneous administration in rats, using a newly developed HPLC-UV bioanalytical method."	( An integrative pharmacokinetic and pharmacodynamic study of the 5-HT1A receptor antagonist (S)-UH-301 in the rat. Lewander, T; Yan, H; Yu, H, 2002)	0.31
" To address this issue, we conducted a pharmacokinetic study with 164 patients with sporadic Parkinson's disease."	( Body weight influences pharmacokinetics of levodopa in Parkinson's disease. Arabia, G; Bagalà, A; Bastone, L; Bonavita, S; Caracciolo, M; Crescibene, L; Di Costanzo, A; Gambardella, A; Nicoletti, G; Quattrone, A; Scornaienchi, M; Zappia, M, )	0.39
" This entails evaluating the pharmacokinetics and pharmacodynamic actions of the drug regimens used and possibly, dosage form and route of administration of the drugs."	( Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa. Okereke, CS, )	0.33
" Plasma concentrations of levodopa and 3-O-methyldopa were measured by high-performance liquid chromatography for pharmacokinetic evaluation."	( Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy volunteers. Crevoisier, C; Metzger, B; Monreal, A; Nilsen, T, 2003)	0.86
"We conducted a pharmacokinetic study in 164 patients with sporadic Parkinson's disease (PD) to address the relationship between body weight and levodopa pharmacokinetics."	( Body weight, levodopa pharmacokinetics and dyskinesia in Parkinson's disease. Arabia, G; Bagalà, A; Bastone, L; Bosco, D; Caracciolo, M; Crescibene, L; Quattrone, A; Scornaienghi, M; Zappia, M, 2002)	0.88
" Plasma concentrations of levodopa and 3-O-methyldopa were determined by high-performance liquid chromatography for pharmacokinetic evaluation."	( Effects of food on the pharmacokinetics of levodopa in a dual-release formulation. Calvi-Gries, F; Crevoisier, C; Nilsen, T; Zerr, P, 2003)	0.88
" The elimination half-life of cabergoline estimated from urinary data of healthy subjects ranges between 63 and 109 hours."	( Clinical pharmacokinetics of cabergoline. Bonuccelli, U; Del Dotto, P, 2003)	0.32
" Cmax (maximal L-DOPA concentration reached) was 3161 +/- 345 ng/ml for Sinemet and 3274 +/- 520 ng/ml for Grifoparkin (NS)."	( [Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study]. Chaná, P; Fierro, A; Reyes-Parada, M; Sáez-Briones, P, 2003)	0.57
" To measure the maximal concentration (Cmax), time to Cmax (tmax), and area under the curve (AUC) of plasma levodopa, etilevodopa, and carbidopa, blood samples were drawn before drug administration and at intervals up to 240 minutes thereafter."	( Pharmacokinetics of etilevodopa compared to levodopa in patients with Parkinson's disease: an open-label, randomized, crossover study. Djaldetti, R; Giladi, N; Hassin-Baer, S; Melamed, E; Shabtai, H, )	0.65
"The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinson's disease (PD) patients."	( Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients. Barbato, L; Bolner, A; Caraceni, T; Nordera, G; Stocchi, F, 2004)	0.74
"This study investigated the tolerability and the pharmacokinetic and pharmacodynamic interactions between single oral administration of BIA 3-202 (50 mg, 100 mg, 200 mg, and 400 mg), a novel catechol-O-methyltransferase (COMT) inhibitor, and standard carbidopa/levodopa 25 mg/100 mg (Sinemet 25/100) in healthy adult volunteers."	( Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/carbidopa. Almeida, L; Falcão, A; Loureiro, A; Machado, R; Maia, J; Silveira, P; Soares-da-Silva, P; Torrão, L; Vaz-da-Silva, M; Wright, L, )	0.53
" The aim was to determine whether delayed entacapone administration may prolong CR L-dopa half-life in comparison to the co-administration modality."	( Temporal administration of entacapone with slow release L-dopa: pharmacokinetic profile and clinical outcome. Bassi, A; Brusa, L; Fedele, E; Giacomini, P; Lunardi, G; Pierantozzi, M; Stanzione, P, 2004)	0.32
" Pharmacokinetic parameters for apomorphine (C(max), AUC, t(max), t(1/2)) were unchanged by the administration of entacapone, and changes in both the tapping test and AIMS score were similar with all treatments (entacapone 200 mg, entacapone 400 mg, and placebo)."	( Safety of entacapone and apomorphine coadministration in levodopa-treated Parkinson's disease patients: pharmacokinetic and pharmacodynamic results of a multicenter, double-blind, placebo-controlled, cross-over study. Debilly, B; Durif, F; Lees, AJ; Rascol, O; Zijlmans, JC, 2004)	0.57
" Blood samples were collected before, during and after the 15 doses of donepezil HCl for pharmacokinetic (PK) assessments."	( Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. Cullen, EI; Hahne, WA; Kirby, L; Kumar, D; Okereke, CS; Pratt, RD, 2004)	0.58
" The pharmacokinetic evaluation was repeatedly performed 1 week later in the same way except for adding 200 mg AsA to the tablet."	( The effect of ascorbic acid on the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Hamamoto, M; Katayama, Y; Nagayama, H; Nito, C; Ueda, M; Yamaguchi, H, )	0.38
" The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half-life, and the area under the plasma concentration-time curve."	( Genetic polymorphism of catechol-O-methyltransferase and levodopa pharmacokinetic-pharmacodynamic pattern in patients with Parkinson's disease. Albani, F; Baruzzi, A; Contin, M; Martinelli, P; Mochi, M; Riva, R, 2005)	0.98
" The method has been successfully used to study the pharmacokinetics of levodopa in vivo; the values of the pharmacokinetics parameters Cmax, AUC(0-t) and Tmax were 16."	( Microdialysis sampling and high-performance liquid chromatography with chemiluminescence detection for in-vivo on-line determination and study of the pharmacokinetics of levodopa in blood. Deyong, H; Funan, C; Yingxue, Z; Zhujun, Z, 2005)	0.76
"Human pharmacokinetic parameters are often predicted prior to clinical study from in vivo preclinical pharmacokinetic data."	( Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. Jolivette, LJ; Ward, KW, 2005)	0.33
" Current evidence suggests that these motor complications are related to the relatively short half-life of levodopa and its potential to induce pulsatile stimulation of striatal dopamine receptors."	( Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Olanow, CW; Ruggieri, S; Stocchi, F; Vacca, L, 2005)	0.84
"To investigate the specific pharmacokinetic changes associated with the benefits of levodopa infusion."	( Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Olanow, CW; Ruggieri, S; Stocchi, F; Vacca, L, 2005)	0.85
" Levodopa pharmacokinetic studies were performed at baseline and 6 months in 3 of these patients."	( Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Olanow, CW; Ruggieri, S; Stocchi, F; Vacca, L, 2005)	1.54
" Results of plasma pharmacokinetic studies demonstrated that compared with oral administration, continuous levodopa infusion was associated with a significant increase in the levodopa area under the curve and avoided the low plasma trough levels seen with oral drug administration."	( Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Olanow, CW; Ruggieri, S; Stocchi, F; Vacca, L, 2005)	0.84
" Pharmacokinetic studies demonstrate that reduced motor complications are associated with avoiding low plasma levodopa trough levels and are not adversely affected by relatively high plasma levodopa concentrations."	( Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Olanow, CW; Ruggieri, S; Stocchi, F; Vacca, L, 2005)	0.84
" In this experimental study we have investigated whether the presence of Plantago ovata husk (water-soluble fiber) modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route at the same time."	( Hydrosoluble fiber (Plantago ovata husk) and levodopa I: experimental study of the pharmacokinetic interaction. Calle, A; Carriedo, D; Diez, MJ; Fernandez, N; Garcia, JJ; Gonzalez, A; Sahagun, A; Sierra, M, 2005)	0.78
" ovata husk modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route with carbidopa (5 mg/kg)."	( Hydrosoluble fiber (Plantago ovata husk) and levodopa II: experimental study of the pharmacokinetic interaction in the presence of carbidopa. Calle, A; Carriedo, D; Diez, MJ; Fernandez, N; Garcia, JJ; Gonzalez, A; Sahagun, A; Sierra, M, 2005)	0.81
"Augmentation, defined as a loss of circadian recurrence with progressively earlier daily onset and increase in the duration, intensity, and anatomy of symptoms, not compatible with the half-life of the drug, is associated with dopaminergic treatment in restless legs syndrome (RLS) patients."	( Polysomnographic and pharmacokinetic findings in levodopa-induced augmentation of restless legs syndrome. Baruzzi, A; Contin, M; Montagna, P; Plazzi, G; Provini, F; Vetrugno, R, 2006)	0.59
" A two-compartment pharmacokinetic model with central volume (V1), peripheral volume (V2), clearance (CL) and inter-compartmental clearance (CL(ic)) was used to fit plasma levodopa concentrations."	( Importance of within subject variation in levodopa pharmacokinetics: a 4 year cohort study in Parkinson's disease. Chan, PL; Holford, NH; Nutt, JG, 2005)	0.79
"The purpose of this analysis is to describe how levodopa pharmacokinetic and pharmacodynamic parameters change over the first 4 years of long-term levodopa treatment in patients with Parkinson's disease."	( Pharmacokinetic and pharmacodynamic changes during the first four years of levodopa treatment in Parkinson's disease. Chan, PL; Holford, NH; Nutt, JG, 2005)	0.81
" Using models for disease progression and pharmacodynamic models for drug effects we have characterized the changes in UPDRS over time to determine the influence of the various drug treatments."	( Disease progression and pharmacodynamics in Parkinson disease - evidence for functional protection with levodopa and other treatments. Chan, PL; Holford, NH; Kieburtz, K; Nutt, JG; Shoulson, I, 2006)	0.55
" As most patients require the superior efficacy of levodopa during the course of their disease, an appreciation of the changing response to levodopa over time and an understanding of the pharmacokinetic principles underlying the development of complications such as wearing-off is essential in the long-term management of the patient."	( The levodopa wearing-off phenomenon in Parkinson's disease: pharmacokinetic considerations. Stocchi, F, 2006)	1.14
" Pharmacokinetic parameters were calculated for both treatments."	( The effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers. Bi, LL; Chen, XY; Jia, YY; Luo, XX; Wen, AD; Zhong, DF, 2007)	0.34
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
" Levodopa pharmacokinetic profiles remain unchanged after multiple doses, and are similar between healthy volunteers and patients and among patients at different stages of disease."	( The pharmacokinetics and pharmacodynamics of levodopa in the treatment of Parkinson's disease. Hsu, A; Khor, SP, 2007)	1.51
"In this study, scintigraphic and pharmacokinetic studies were conducted on 10 healthy, fed volunteers."	( Pharmacoscintigraphic and pharmacokinetic evaluation on healthy human volunteers of sustained-release floating minitablets containing levodopa and carbidopa. Amighi, K; Blocklet, D; Deleuze, P; Goldman, S; Goole, J; Pandolfo, M; Pilcer, G; Van Gansbeke, B; Vanderbist, F, 2008)	0.55
"The pharmacokinetics and pharmacodynamics of levodopa are dominated by two features: the short plasma half-life of the drug and the portion of the antiparkinsonian response that parallels the plasma levodopa levels, the so-called short-duration response."	( Pharmacokinetics and pharmacodynamics of levodopa. Nutt, JG, 2008)	0.87
" Pharmacokinetic (PK) parameters determined for levodopa included Cmin, Cmax, Cmax - Cmin, AUC, t(1/2), and tmax."	( Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily. Ellmén, J; Hänninen, J; Hartikainen, P; Kaakkola, S; Kaasinen, V; Kailajärvi, M; Korpela, K; Kuoppamäki, M; Löyttyniemi, E; Lyytinen, J; Marttila, R; Ruokoniemi, P, 2009)	0.87
"This open-label phase I trial assessed potential pharmacokinetic interactions between oral levodopa/carbidopa and transdermal rotigotine treatment at steady state."	( Lack of pharmacokinetic interactions between transdermal rotigotine and oral levodopa/carbidopa. Andreas, JO; Boekens, H; Braun, M; Cawello, W; Horstmann, R, 2009)	0.8
" Pharmacokinetic parameters C(max), t(max), t(1/2z), mean residence time (MRT), AUC(0-tau), AUC(0-infinity), CL(z)/F and V(z)/F were determined under the non-compartmental model."	( Pharmacokinetic profile of talipexole in healthy volunteers is not altered when it is co-administered with Madopar (co-beneldopa). Hang, TJ; Jia, L; Song, M; Wen, AD; Xu, XF; Yang, L; Zhang, TT, 2009)	0.35
" For talipexole hydrochloride, there were no significant differences in the pharmacokinetic values between the two administrations."	( Pharmacokinetic profile of talipexole in healthy volunteers is not altered when it is co-administered with Madopar (co-beneldopa). Hang, TJ; Jia, L; Song, M; Wen, AD; Xu, XF; Yang, L; Zhang, TT, 2009)	0.35
" There was no significant difference in pharmacokinetic parameters, including t(1/2alpha), t(1/2beta), AUC(0-infinity), CL/F, C(max), t(max) and V/F."	( Genetic polymorphism of catechol O-methyltransferase and pharmacokinetics of levodopa in healthy Chinese subjects. Huang, PF; Ke, M; Lin, CH; Liu, YW; Wang, CL; Xu, Y; Yu, CX, )	0.36
" This study aims to investigate the feasibility of L-dopa nasal delivery systems prepared using maleic acid solution containing 2-hydroxypropyl-beta-cyclodextrin, and to develop pharmacokinetic models."	( Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems. Chun, IK; Gwak, HS; Kang, W; Kim, TK; Lee, YH; Oh, SY, 2009)	0.6
"0] kg/m2) completed the 4 treatment periods and had data available for pharmacokinetic and pharmacodynamic analyses."	( Pharmacokinetic-pharmacodynamic interaction between nebicapone and controlled-release levodopa/benserazide: a single-center, Phase I, double-blind, randomized, placebo-controlled, four-way crossover study in healthy subjects. Almeida, L; Costa, R; Falcão, A; Fernandes-Lopes, C; Loureiro, AI; Machado, R; Nunes, T; Rocha, JF; Soares-da-Silva, P; Torrão, L; Vaz-da-Silva, M; Wright, L, 2009)	0.58
"The aims of the present study were to investigate the pharmacokinetic and pharmacodynamic (pk/pd) relationship of levodopa (l-dopa) in patients with advanced Parkinson disease (PD) and also to evaluate the effect of tolcapone on the pk/pd analysis of l-dopa in 1 patient with severe dyskinesias and fluctuations."	( Pharmacokinetic-pharmacodynamic modeling of levodopa in patients with advanced Parkinson disease. Adamiak, U; Bialecka, M; Gawronska-Szklarz, B; Kaldonska, M; Klodowska-Duda, G; Safranow, K; Wyska, E, 2010)	0.83
"Levodopa is the most effective treatment for Parkinson's disease, so it is important to understand the pharmacokinetic and pharmacodynamic features of this drug."	( Effects of dietary factors on levodopa pharmacokinetics. Diez, MJ; Díez, R; Fernandez, N; Garcia, JJ; Sahagun, AM; Sierra, M, 2010)	2.09
" Finally, the method was successfully applied to support the pharmacokinetic study after L-dopa and its prodrug AEPD were orally administrated to the Sprague-Dawley rats, respectively."	( Simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate in rat plasma by high-performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study. Huang, X; Jiang, W; Lv, C; Lv, L; Shi, X; Wu, L; Xu, C; Zhou, S, 2010)	0.36
" Levodopa plasma half-life is very short, resulting in marked plasma drug concentration fluctuations which are matched, as the disease progresses, to swings in the therapeutic response ("wearing-off" phenomena)."	( Pharmacokinetics of levodopa. Contin, M; Martinelli, P, 2010)	1.59
"The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of a levodopa/carbidopa gel (Duodopa) to examine pharmacological properties of this treatment."	( A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion. Dougherty, M; Groth, T; Karlsson, MO; Nyholm, D; Pålhagen, S; Westin, J; Willows, T, )	0.58
"The investigators conducted a single-dose pharmacokinetic (PK) study of levodopa/carbidopa delivered from novel gastric-retentive extended-release (ER) tablets versus a comparator ER tablet (M-ER) in patients with Parkinson's disease."	( Pharmacokinetics of levodopa/carbidopa delivered from gastric-retentive extended-release formulations in patients with Parkinson's disease. Chen, C; Cowles, VE; Illarioshkin, SN; Stolyarov, ID; Sweeney, M, 2012)	0.93
" The validated method was applied in a pharmacokinetic study with a levodopa/benserazide tablet formulation in healthy volunteers."	( Simultaneous quantitation of levodopa and 3-O-methyldopa in human plasma by HPLC-ESI-MS/MS: application for a pharmacokinetic study with a levodopa/benserazide formulation. Bonfim, RR; Byrro, RM; Cardoso, FF; César, Ida C; da Silva, EP; Gomes, SA; Mundim, IM; Pianetti, GA; Teixeira, Lde S, 2011)	0.9
"This review summarizes the overall pharmacokinetic profile of pramipexole for both the IR and ER formulations."	( Pharmacokinetic evaluation of pramipexole. Antonini, A; Calandrella, D, 2011)	0.37
" Blood samples were collected for pharmacokinetic (PK) analysis, and a finger-tapping test was performed to assess pharmacodynamics."	( Pharmacokinetics and pharmacodynamics of gastroretentive delivery of levodopa/carbidopa in patients with Parkinson disease. Chen, C; Cowles, VE; Illarioshkin, SN; Stolyarov, ID; Sweeney, M, )	0.37
" The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets."	( Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Aquilonius, SM; Bäckström, T; Ehrnebo, M; Gomes-Trolin, C; Lewander, T; Nyholm, D; Nyström, C; Panagiotidis, G, )	0.79
"The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets."	( Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Aquilonius, SM; Bäckström, T; Ehrnebo, M; Gomes-Trolin, C; Lewander, T; Nyholm, D; Nyström, C; Panagiotidis, G, )	0.89
" All patients underwent levodopa pharmacokinetic study and the gastric emptying study using (13)C-octanoic acid expiration breath test."	( Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease. Doi, H; Kishi, M; Masaka, T; Sakakibara, R; Sato, M; Takahashi, O; Tateno, A; Tateno, F; Tsuyusaki, Y, 2012)	1.14
" Half-life was 58."	( L-DOPA pharmacokinetics in the MPTP-lesioned macaque model of Parkinson's disease. Brotchie, JM; Fox, SH; Huot, P; Johnston, TH; Koprich, JB, 2012)	0.38
" L-DOPA t(max) and half-life are also similar to those reported in human."	( L-DOPA pharmacokinetics in the MPTP-lesioned macaque model of Parkinson's disease. Brotchie, JM; Fox, SH; Huot, P; Johnston, TH; Koprich, JB, 2012)	0.38
" This was the first study designed to characterize the full pharmacokinetic profiles of levodopa, carbidopa, and levodopa metabolite, 3-O-methyldopa (3-OMD) with 16-h LCIG infusion."	( Pharmacokinetics of levodopa, carbidopa, and 3-O-methyldopa following 16-hour jejunal infusion of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients. Chatamra, K; Dutta, S; Johansson, A; Locke, C; Nyholm, D; Odin, P; Othman, AA, 2013)	0.94
"A pharmacodynamic model is presented to describe the motor effects (tapping rate, Unified Parkinson's Disease Rating Scale [UPDRS] Part III, and investigator-rating of ON/OFF, including dyskinesia) of levodopa (LD) in patients with advanced idiopathic Parkinson's disease (PD) treated with immediate-release (IR) carbidopa-levodopa (CD-LD) or an extended-release (ER) formulation of CD-LD (IPX066)."	( Population pharmacodynamics of IPX066: an oral extended-release capsule formulation of carbidopa-levodopa, and immediate-release carbidopa-levodopa in patients with advanced Parkinson's disease. Gupta, S; Hsu, A; Mao, Z; Modi, NB, 2013)	0.8
" A new formulation, an orally disintegrating tablet (ODT), has recently been introduced to overcome these pharmacokinetic problems by avoiding its presystemic metabolism."	( The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson's disease. Magyar, K; Szökő, E; Tábi, T; Vécsei, L, 2013)	0.39
"The authors summarize the pharmacokinetic and clinical efficacy data of selegiline ODT and compare them with the more conventional oral selegiline."	( The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson's disease. Magyar, K; Szökő, E; Tábi, T; Vécsei, L, 2013)	0.39
"Selegiline ODT shows a clear pharmacokinetic advantage over the conventional form."	( The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson's disease. Magyar, K; Szökő, E; Tábi, T; Vécsei, L, 2013)	0.39
" Istradefylline , a xanthine derivative, has the longest half-life of all the currently available A2A adenosine receptor antagonists; it can successfully permeate through the blood-brain barrier and has a high human A2A adenosine receptor affinity."	( Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations. Müller, T, 2013)	0.39
" Specifically, the article reviews the clinical and pharmacokinetic information available to elucidate its therapeutic potential."	( Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations. Müller, T, 2013)	0.39
" l-dopa has a complex pharmacokinetic behavior and causes long-term behavioral and metabolic side effects."	( Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations. Müller, T, 2013)	0.39
" Pharmacokinetic trials of oral LD/dopa decarboxylase inhibitor (DDCI) formulations with and without the catechol-O-methyltransferase inhibitor, entacapone, showed that repeated administration with entacapone causes an increase in both the maximum concentration (Cmax) and time to Cmax (Tmax) of LD."	( Pharmacokinetic considerations for the use of levodopa in the treatment of Parkinson disease: focus on levodopa/carbidopa/entacapone for treatment of levodopa-associated motor complications. Müller, T, )	0.39
" The pharmacokinetic analyses demonstrated relatively low bioavailability for L-dopa and adequate plasma levels of pramipexole, even at baseline, on a stable daily dose."	( Therapeutic response to pramipexole in a patient with multiple system atrophy with predominant parkinsonism: positron emission tomography and pharmacokinetic assessments. Ishii, K; Katayama, Y; Nagayama, H; Nakajima, N; Nishiyama, Y; Ueda, M, 2013)	0.39
"Opicapone increased levodopa systemic exposure by 2-fold not changing Cmax values and reduced both 3-O-methyldopa (3-OMD) exposure and Cmax values by 5-fold."	( Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor. Bonifácio, MJ; Soares-da-Silva, P; Sutcliffe, JS; Torrão, L; Wright, LC, 2014)	0.99
"The objective of this study was to investigate the pharmacokinetic characteristics of levodopa (L-dopa) from nasal powder formulations using highly water-soluble levodopa methyl ester hydrochloride (LDME)."	( Pharmacokinetic evaluation of formulated levodopa methyl ester nasal delivery systems. Chun, IK; Gwak, HS; Kim, KH; Lee, KE; Lee, YH; Rhie, JY; Yoon, IK, 2014)	0.89
" The final model was internally evaluated using stochastic simulations and bootstrap and externally evaluated using sparse pharmacokinetic data from 311 subjects treated in a long term safety study of LCIG."	( Population pharmacokinetics of levodopa in subjects with advanced Parkinson's disease: levodopa-carbidopa intestinal gel infusion vs. oral tablets. Dutta, S; Othman, AA, 2014)	0.69
" The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone."	( Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations. Falcão, A; Lopes, N; Nunes, T; Pinto, R; Rocha, JF; Santos, A; Soares-da-Silva, P; Vaz-da-Silva, M; Wright, LC, 2014)	0.93
" Changes of small magnitude but with possible clinical impact were found according to tmax and Cmax that tended to be lower in HP- patients and AUC0-t that was larger in the HP+ group."	( Pharmacokinetics of levodopa in patients with Parkinson disease and motor fluctuations depending on the presence of Helicobacter pylori infection. Adamiak-Giera, U; Białecka, M; Gawrońska-Szklarz, B; Madaliński, MH; Narożańska, E; Robowski, P; Schinwelski, M; Sołtan, W; Sławek, J, )	0.45
"Levodopa Cmax was very similar in the initial situation (603."	( A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters. Anguera-Vila, A; Calle-Pardo, A; Carriedo-Ule, D; Diez-Liebana, MJ; Fernandez-Martinez, MN; Garcia-Vieitez, JJ; Hernandez-Echevarria, L; Sahagún-Prieto, AM; Sierra-Vega, M, 2014)	2.06
" In the presence of levodopa, gastric emptying is interrupted at times associated with double-peaks in pharmacokinetic profiles."	( Empirical and semi-mechanistic modelling of double-peaked pharmacokinetic profile phenomenon due to gastric emptying. Aarons, L; Ogungbenro, K; Pertinez, H, 2015)	0.74
"In Japanese subjects with advanced PD, LCIG resulted in an improved pharmacokinetic profile that appeared to be associated with reduced motor complications compared with LC-oral."	( Jejunal Infusion of levodopa-carbidopa intestinal gel versus oral administration of levodopa-carbidopa tablets in japanese subjects with advanced Parkinson's disease: pharmacokinetics and pilot efficacy and safety. Benesh, J; Chatamra, K; Dutta, S; Mohamed, ME; Nagai, M; Othman, AA; Yanagawa, M, 2015)	0.74
" The main levodopa pharmacodynamic variables were the maximum percentage increase in tapping frequency over baseline values (ΔTapmax %) and the area under the tapping effect-time curve (AUCTap)."	( Pharmacodynamics of a low subacute levodopa dose helps distinguish between multiple system atrophy with predominant Parkinsonism and Parkinson's disease. Calandra-Buonaura, G; Capellari, S; Contin, M; Cortelli, P; Doria, A; Guaraldi, P; Lopane, G; Martinelli, P, 2016)	1.11
" Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt."	( Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers. Gupta, S; Hsu, A; Modi, NB; Yao, HM, )	0.13
" From the comparison of the results of pharmacokinetic study before and after taking LD/CD or LD/CD/soy, the estimated marginal mean (EMM) of HVA after LD/CD/soy increased in the PD group."	( Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens. Ito, H; Koh, J; Kondo, T; Nagashima, Y; Sakata, M, 2016)	0.68
" In order to simultaneously determine levodopa and 1,1-dimethyl-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (MD01) in rat plasma, an improved LC-MS/MS method was developed and validated for a pharmacokinetic study in rats orally administered levodopa or Mucuna pruriens extract (MPE)."	( Development and validation of an LC-MS/MS method for simultaneous quantification of levodopa and MD01 in rat plasma and its application to a pharmacokinetic study of mucuna pruriens extract. Chen, C; Cheng, Z; Deng, L; Huang, J; Jiang, H; Liu, J; Yang, G; Zhang, F, 2016)	0.93
"To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa."	( Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics. Almeida, L; Bonifácio, MJ; Falcão, A; Fauchoux, N; Loureiro, AI; Nunes, T; Pinto, R; Rocha, JF; Santos, A; Sicard, É; Soares-da-Silva, P, 2017)	1.07
"This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson's disease."	( Levodopa/carbidopa microtablets in Parkinson's disease: a study of pharmacokinetics and blinded motor assessment. Aquilonius, SM; Askmark, H; Bergquist, F; Constantinescu, R; Ericsson, A; Lycke, S; Medvedev, A; Memedi, M; Nyholm, D; Ohlsson, F; Senek, M; Spira, J; Westin, J, 2017)	2.14
" We present in this report the comparative pharmacokinetic profiles of LCIG and LC-oral from this pivotal study."	( Levodopa-Carbidopa Intestinal Gel Pharmacokinetics: Lower Variability than Oral Levodopa-Carbidopa. Chatamra, K; Dutta, S; Locke, C; Othman, AA; Rosebraugh, M, 2017)	1.9
"  This review presents a synthesis of the population pharmacokinetic and pharmacodynamic models of levodopa described in Parkinson's disease."	( Levodopa in Parkinson's Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis. Azulay, JP; Blin, O; Guilhaumou, R; Marsot, A, 2017)	2.11
" Different pharmacodynamic effects were described: UPDRS, Tapping, Dyskinesia, CURSΣ and treatment response scale."	( Levodopa in Parkinson's Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis. Azulay, JP; Blin, O; Guilhaumou, R; Marsot, A, 2017)	1.9
" New pharmacokinetic and/or pharmacodynamic population modelling studies could be consider to improve future models and decrease variability, to better understand the evolution of patients with Parkinson's disease treated by levodopa."	( Levodopa in Parkinson's Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis. Azulay, JP; Blin, O; Guilhaumou, R; Marsot, A, 2017)	2.08
" Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD."	( Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson's disease. Kostić, V; Kresojević, N; Svetel, M; Tomić, A, 2018)	0.48
" The pharmacodynamic endpoint did not meet the pre-specified criteria for significant improvement."	( A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, in Subjects with Idiopathic Parkinson's Disease. DeMartinis, N; Duvvuri, S; Gurrell, R; Sun, P, 2018)	0.48
" Moreover, the bioanalytical method was applied to a pharmacokinetic study in healthy volunteers."	( Sensitive LC-MS/MS method for quantitation of levodopa and carbidopa in plasma: application to a pharmacokinetic study. Brandão, AH; Davanço, MG; de Campos, DR; Ferreira, MS; Gabbai, JJ; Júnior, PS; Martho, AC; Meulman, J; Noboli, AC; Pepi, GT; Previde, N; Riccio, MF, 2018)	0.74
" We proposed mechanisms for the interaction between LDCD and MgO and conducted pharmacokinetic studies on rats and humans."	( Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Hirakawa, M; Hirota, T; Ieiri, I; Irie, S; Kashihara, Y; Kimura, M; Kubota, T; Matsuki, S; Terao, Y; Yoda, K, 2019)	0.51
" We conducted pharmacokinetic interaction studies of MgO and LDCD on rats and healthy volunteers."	( Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Hirakawa, M; Hirota, T; Ieiri, I; Irie, S; Kashihara, Y; Kimura, M; Kubota, T; Matsuki, S; Terao, Y; Yoda, K, 2019)	0.51
"This is the first study to show a clear pharmacokinetic interaction between LDCD and MgO in humans."	( Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Hirakawa, M; Hirota, T; Ieiri, I; Irie, S; Kashihara, Y; Kimura, M; Kubota, T; Matsuki, S; Terao, Y; Yoda, K, 2019)	0.51
"Compared with Rytary and IR CD-LD, IPX203 had a longer pharmacodynamic effect consistent with LD pharmacokinetics for the 3 treatments."	( Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules. Gupta, S; Khanna, S; Mittur, A; Modi, NB; Rubens, R, )	0.33
" Areas covered: This narrative review aims to describe the pharmacokinetic characteristics of the available reversible and irreversible monoamine oxidase B inhibitors for the treatment of Parkinson's disease in daily practice."	( Pharmacokinetics of monoamine oxidase B inhibitors in Parkinson's disease: current status. Möhr, JD; Müller, T, 2019)	0.51
"We conducted pharmacokinetic experiments in pigs, mice, and humans to characterize effects of continuous subcutaneous CD delivery co-administered with LD as compared with oral LD/CD administration on LD pharmacokinetics."	( Subcutaneous Administration of Carbidopa Enhances Oral Levodopa Pharmacokinetics: A Series of Studies Conducted in Pigs, Mice, and Healthy Volunteers. Caraco, Y; LeWitt, PA; Nemas, M; Oren, S; Shaltiel-Karyo, R; Weinstock, I; Yacoby-Zeevi, O; Zawaznik, E, )	0.38
" Pharmacokinetic and motor assessments were conducted on days 1 and 15 of each treatment period."	( Pharmacodynamics, Efficacy, and Safety of IPX203 in Parkinson Disease Patients With Motor Fluctuations. Dinh, P; Gupta, S; Mittur, A; Modi, NB; Rubens, R, )	0.13
"While several generic preparations of levodopa/carbidopa and levodopa/benserazide (LBD) are currently available, pharmacokinetic (PK) equivalence and therapeutic equivalence studies with levodopa generics are not available in Italy."	( Clinical and pharmacokinetics equivalence of multiple doses of levodopa benserazide generic formulation vs the originator (Madopar). Alessandroni, J; Bonassi, S; Bravi, D; Casali, M; Fossati, C; Grassini, P; Ialongo, C; Onofrj, M; Radicati, FG; Stocchi, F; Torti, M; Vacca, L, 2019)	1.02
" Using a holistic approach, a pharmacokinetic model of levodopa was combined to a dopamine dynamics and a neurocomputational model of basal ganglia."	( Nonlinear pharmacodynamics of levodopa through Parkinson's disease progression. Lévesque, D; Nekka, F; Robaey, P; Ursino, M; Véronneau-Veilleux, F, 2020)	1.09
" We combined a pharmacokinetic model of levodopa to a model of dopamine's kinetics and a neurocomputational model of basal ganglia."	( An integrative model of Parkinson's disease treatment including levodopa pharmacokinetics, dopamine kinetics, basal ganglia neurotransmission and motor action throughout disease progression. Nekka, F; Robaey, P; Ursino, M; Véronneau-Veilleux, F, 2021)	1.13
" In this study, a rapid High Performance Liquid Chromatography (HPLC) method was validated in presence of internal standard to determine pharmacokinetic parameters following levodopa administration to rats in three different intravenous solution, intranasal solution and intranasal thermosensitive gel groups."	( Rapid High-Performance Liquid Chromatography Method for Levodopa Quantitation at Low UV Wavelength: Application of Pharmacokinetics Study in Rat Following Intranasal Delivery. Alipour, S; Mohammadi, Z; Parhizkar, E, 2021)	1.06
" Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples."	( Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration. De la Paz, E; Huang, N; Litvan, I; Longardner, K; Mahato, K; Moon, JM; Sempionatto, JR; Sonsa-Ard, T; Teymourian, H; Wang, J, 2021)	0.62
"Inhibiting catechol-O-methyltransferase extends the plasma half-life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) experiencing motor fluctuations."	( Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease. Antonini, A; Ferreira, JJ; Guimarães, B; Moreira, J; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P; Stocchi, F, 2022)	1.26
" Despite a 100 mg lower total levodopa/carbidopa daily dose, adding opicapone 50 mg at least doubled the levodopa plasma half-life and minimal concentrations, with a significant ≈30% increase in total exposure."	( Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease. Antonini, A; Ferreira, JJ; Guimarães, B; Moreira, J; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P; Stocchi, F, 2022)	1.32
" Despite the lower levodopa dose, modifying the levodopa pharmacokinetic profile with opicapone was associated with decreased off time and increased on time."	( Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease. Antonini, A; Ferreira, JJ; Guimarães, B; Moreira, J; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P; Stocchi, F, 2022)	1.36
"A double-blind, placebo-controlled, randomized, crossover, phase I, pharmacokinetic study with 25 healthy volunteers was conducted."	( Effect of Carbidopa Dose on Levodopa Pharmacokinetics With and Without Catechol-O-Methyltransferase Inhibition in Healthy Subjects. Ellmén, J; Kuoppamäki, M; Rouru, J; Sjöstedt, N; Tuunainen, J; Vahteristo, M; Yliperttula, M, 2023)	1.2
" Theoretical pharmacokinetic simulations suggested that the plasma profile of oral IR levodopa can be even further improved by optimizing AADC and COMT inhibition."	( Effect of Carbidopa Dose on Levodopa Pharmacokinetics With and Without Catechol-O-Methyltransferase Inhibition in Healthy Subjects. Ellmén, J; Kuoppamäki, M; Rouru, J; Sjöstedt, N; Tuunainen, J; Vahteristo, M; Yliperttula, M, 2023)	1.43
" At steady-state (day 14), opicapone Cmax (peak plasma concentration) and AUC 0-last (area under the curve-time curve) were 459 ± 252 ng/mL and 2022 ± 783 ng/mL·h, respectively."	( Opicapone Pharmacokinetics and Effects on Catechol- O -Methyltransferase Activity and Levodopa Pharmacokinetics in Patients With Parkinson Disease Receiving Carbidopa/Levodopa. Jimenez, R; Kieburtz, KD; Klepitskaya, O; LeWitt, P; Liang, GS; Loewen, G; Olanow, CW; Olson, K, )	0.35

Compound-Compound Interactions

The administration of Resagiline combined with levodopa and benserazide hydrochloride can significantly lower the body's serum Hcy level, significantly raise IGF-1 levels, and significantly improve motor function in patients with Parkinson's disease. These results suggest that pramipexole could be administered with a reduced dose oflevodopa to minimize dyskinesia.

Excerpt	Reference	Relevance
"The effects of carbidopa combined with levodopa (carbidopa/levodopa) and levodopa alone on the cardiovascular system of patients with Parkinson's disease were evaluated."	( Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone on the cardiovascular system of patients with parkinson's disease. Leibowitz, M; Lieberman, A, 1975)	0.76
" With the combination medication, levodopa-carbidopa, on an average 420 mg/42 mg combined with 950 mg of levodopa in slow release form, a statistically significant improvement in parkinsonian signs could be achieved without any worsening of the side effects."	( Effect of a slow release preparation of levodopa on Parkinson's disease in combination with a peripheral decarboxylase inhibitor. Hokkanen, E; Myllylä, VV; Saarinen, A; Tokola, O, 1978)	0.8
" Levodopa treatment, alone or in combination with two different dopa-decarboxylase inhibitors, benserazide and carbidopa, does not modify the renin response to posture or to frusemide."	( Effects of levodopa alone and in combination with dopa-decarboxylase inhibitors on plasma renin activity in patients with Parkinson's disease. Dessi'-Fulgheri, P; Glorioso, N; Monaco, F; Rappelli, A; Tedde, R, 1978)	1.56
"Since L-dopa in combination with a decarboxylase inhibitor is currently the most effective therapy available for treatment of Parkinson's disease, the authors compare the actual causes of death in a large series of treated Parkinson patients with a normal population and with previous studies."	( Mortality among Parkinson patients treated with L-dopa combined with a decarboxylase inhibitor. Siegfried, J; Zumstein, H, 1976)	0.26
"Eighty-one Parkinsonic patients were treated with L-dopa alone and/or combined with Ro4-4602, during 27 to 60 months."	( [5 years of experience in the treatment of parkinsonism with L-dopa and its combination with Ro4-4602]. Chouza, C; Gomensoro, JB; Romero, S, 1976)	0.26
"The further therapeutic benefit of piribedil when combined with amantadine or Levodopa was studied by a double-blind, cross-over trial in 15 patients with Parkinson's disease."	( Piribedil (ET 495) in the treatment of Parkinson's disease combined with amantadine or levodopa. Callaghan, N; Fitzpatrick, E; O'Mahony, JB, 1975)	0.71
" (1) Concentrations of dopa and dopamine in plasma and brain were measured in cats following intraperitoneal injection of L-dopa alone (100 mg/kg) or combined with MK-486 (10 mg/kg)."	( L-dopa therapy combined with peripheral decarboxylase inhibitor (MK-486) in Parkinsonism. Kishikawa, H; Ohmoto, T, 1975)	0.25
"5 g of levodopa daily for up to six months and in 30 patients receiving levodopa (800-1,000 mg) combined with a dopa decarboxylase inhibitor, benserazide (200-250 mg)."	( Urinary excretion of monoamines and their metabolites in patients with Parkinson's disease. Response to long-term treatment with levodopa alone or in combination with a dopa decarboxylase inhibitor and clinical correlations. Rinne, UK; Siirtola, T; Sonninen, V, 1975)	0.91
" Careful preoperative evaluation and screening combined with limited prescribing can help to limit the magnitude of this problem."	( Drug interactions in anesthesia. Cooke, JE, 1985)	0.27
"In an experiment on Wistar male rats the authors studied the effects of teturam, diethyldithiocarbamate and Esperale in combination with L-DOPA on the consumption of alcohol and metabolism of biogenic amines in the brain."	( [Increased efficacy of teturam combined with L-DOPA in experimental alcoholism in the rat]. Bobkova, NV; Gromova, EA; Khesin, II; Plakkhinas, LA; Tokareva, AE, 1986)	0.27
"In an open study 25 depressed patients were treated with L-5-hydroxytryptophan (L-5-HTP) either alone or in combination with a peripheral decarboxylase inhibitor."	( L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Battegay, R; Gastpar, M; Zmilacher, K, 1988)	0.27
" Brief information on the following reports of drug-drug interactions is given in this article with the intention of giving these reports wider publicity and, possibly, encouraging further observation and research to establish or disprove their validity in a larger and wider range of patients or volunteer subjects."	( Early reports on drug interactions. D'Arcy, PF, 1983)	0.27
"Lisuride, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was combined with levodopa in 20 patients with advanced Parkinson disease who were no longer responding satisfactorily to levodopa, including 14 patients with "on-off' phenomena."	( Lisuride combined with levodopa in advanced Parkinson disease. Goldstein, M; Gopinathan, G; Leibowitz, M; Lieberman, AN; Neophytides, A; Pact, V; Walker, R, 1981)	0.79
"Bromocriptine (Parlodel) was given for 2 years to 17 parkinsonian patients showing inadequate response to treatment over a mean of 7 years with levodopa combined with a decarboxylase inhibitor."	( Bromocriptine combined with levodopa in Parkinson's disease. Gauthier, G; Martins da Silva, A, 1982)	0.76
"We examined whether or not the antiparkinsonian activity of talipexole (B-HT 920, 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) could be optimised by combination with L-3,4-dihydroxyphenylalanine (L-dopa)."	( Antiparkinsonian activity of talipexole in MPTP-treated monkeys: in combination with L-dopa and as chronic treatment. Fukuda, T; Irifune, M; Nomoto, M, 1994)	0.29
"In order to compare two titrations of Parlodel in early combination with levodopa in the treatment of Parkinson's disease a multicentre randomized open study was performed with a fast titration in group A (15 mg/day for 3 weeks) and slow in group B (15 mg/day for 5 weeks)."	( [Parlodel in early combination with levodopa in the treatment of Parkinson disease. Comparison of 2 dosage forms]. Bourdeix, I; Chaumet-Riffaud, PD; Goulley, F; Wolmark, Y, )	0.64
"To compare effectiveness of levodopa and levodopa combined with selegiline in treating early, mild Parkinson's disease."	( Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. Lees, AJ, 1995)	0.83
"Treatment with levodopa and dopa decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in combination with selegiline (arm 2)."	( Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. Lees, AJ, 1995)	0.89
"Levodopa in combination with selegiline seemed to confer no clinical benefit over levodopa alone in treating early, mild Parkinson's disease."	( Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. Lees, AJ, 1995)	1.98
" When combined with N-0923, nicotine did not further enhance its effects."	( Nicotine alone and in combination with L-DOPA methyl ester or the D(2) agonist N-0923 in MPTP-induced chronic hemiparkinsonian monkeys. Domino, EF; Ni, L; Zhang, H, 1999)	0.3
"The effects of ketamine, a noncompetitive antagonist of NMDA receptors, on the striatal dopaminergic system were evaluated multiparametrically in the monkey brain using high-resolution positron emission tomography (PET) in combination with microdialysis."	( Ketamine decreased striatal [(11)C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: multiparametric PET studies combined with microdialysis analysis. Fukumoto, D; Harada, N; Kakiuchi, T; Nishiyama, S; Ohba, H; Sato, K; Tsukada, H, 2000)	0.31
" For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy."	( Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Fries, W; Koenig, E; Müller, F; Scheidtmann, K, 2001)	0.96
"A single dose of levodopa is well tolerated and, when given in combination with physiotherapy, enhances motor recovery in patients with hemiplegia."	( Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Fries, W; Koenig, E; Müller, F; Scheidtmann, K, 2001)	1.05
" In the present study, we examined tissues from normal macaque monkeys treated for 13 weeks with high doses of L-DOPA (in combination with the peripheral decarboxylase inhibitor, carbidopa) and/or the COMT inhibitor, entacapone."	( Chronic high dose L-DOPA alone or in combination with the COMT inhibitor entacapone does not increase oxidative damage or impair the function of the nigro-striatal pathway in normal cynomologus monkeys. Halliwell, B; Jenner, P; Lyras, L; McKenzie, G; Pearce, RK; Zeng, BY, 2002)	0.31
" When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron."	( [Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs]. Kamimura, N; Murayama, N; Sunagane, N; Terawaki, Y; Uruno, T; Yoshinobu, E, 2005)	0.76
"In two 4-week polysomnography pilot studies with 10 patients each, we investigated the efficacy of oral lisuride as monotherapy in de novo RLS patients as well as in combination with levodopa in advanced RLS."	( Lisuride treatment of restless legs syndrome: first studies with monotherapy in de novo patients and in combination with levodopa in advanced disease. Benes, H; Deissler, A; Engfer, A; Kohnen, R; Rodenbeck, A, 2006)	0.73
"Fifty cases in a treatment group were treated by acupuncture combined with madopar, and 30 cases in a control group treated by madopar only."	( Fifty cases of Parkinson's disease treated by acupuncture combined with madopar. Ren, XM, 2008)	0.35
" We now examine the effects of the novel high affinity, dopamine D(2) receptor partial agonist, aplindore alone and in combination with L-dopa in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset."	( The dopamine D(2) receptor partial agonist aplindore improves motor deficits in MPTP-treated common marmosets alone and combined with L-dopa. Andree, TH; Hansard, M; Hoffman, DC; Hurtt, MR; Jackson, MJ; Jenner, P; Kehne, JH; Pitler, TA; Smith, LA; Stack, G, 2010)	0.36
" These results suggest that pramipexole could be administered with a reduced dose of levodopa to minimize dyskinesia in Parkinson's disease while maintaining therapeutic efficacy."	( Pramipexole combined with levodopa improves motor function but reduces dyskinesia in MPTP-treated common marmosets. Jackson, MJ; Jenner, P; Olanow, CW; Rose, S; Tayarani-Binazir, KA, 2010)	0.88
"An HPLC method combined with second-order calibration based on alternating trilinear decomposition (ATLD) algorithm has been developed for the quantitative analysis of levodopa (LVD), carbidopa (CBD) and methyldopa (MTD) in human plasma samples."	( Quantitative analysis of levodopa, carbidopa and methyldopa in human plasma samples using HPLC-DAD combined with second-order calibration based on alternating trilinear decomposition algorithm. Fu, HY; Li, SF; Li, YN; Nie, JF; Wu, HL; Yu, RQ; Yu, YJ, 2010)	0.86
" However, once dyskinesia has developed, dopamine agonists administered with l-dopa exacerbate involuntary movements."	( The partial dopamine agonist pardoprunox (SLV308) administered in combination with l-dopa improves efficacy and decreases dyskinesia in MPTP treated common marmosets. Jackson, MJ; Jenner, P; McCreary, AC; Rose, S; Tayarani-Binazir, K, 2010)	0.36
"To determine the efficacy of standard levodopa combined with controlled release levodopa and entacapone in controlling end-of-dose symptoms in Parkinson's disease."	( A single-blind cross over study investigating the efficacy of standard and controlled release levodopa in combination with entacapone in the treatment of end-of-dose effect in people with Parkinson's disease. Danoudis, M; Iansek, R, 2011)	0.86
"A single-blind cross over design was used to compare the duration of action for three pharmacological combinations: standard levodopa (L/DDC); standard levodopa combined with entacapone (L/DDC/E); and standard levodopa combined with controlled release levodopa (CR) and entacapone (L/DDC/CR/E)."	( A single-blind cross over study investigating the efficacy of standard and controlled release levodopa in combination with entacapone in the treatment of end-of-dose effect in people with Parkinson's disease. Danoudis, M; Iansek, R, 2011)	0.79
" We sought to prospectively study the effects of levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy on mood and cognition following stroke in human subjects."	( Effect of methylphenidate and/or levodopa combined with physiotherapy on mood and cognition after stroke: a randomized, double-blind, placebo-controlled trial. Delbari, A; Lokk, J; Salman-Roghani, R, 2011)	0.9
"A 15-day course of daily MPH + LD combined with physiotherapy over a 3-week period was safe and significantly improved mood status in ischemic stroke patients."	( Effect of methylphenidate and/or levodopa combined with physiotherapy on mood and cognition after stroke: a randomized, double-blind, placebo-controlled trial. Delbari, A; Lokk, J; Salman-Roghani, R, 2011)	0.65
" VU0364770 showed efficacy alone or when administered in combination with L-DOPA or an adenosine 2A (A2A) receptor antagonist currently in clinical development (preladenant)."	( The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease. Amalric, M; Blobaum, AL; Bode, J; Bridges, TM; Bubser, M; Conn, PJ; Daniels, JS; Dickerson, JW; Engers, DW; Hopkins, CR; Italiano, K; Jadhav, S; Jones, CK; Lindsley, CW; Morrison, RD; Niswender, CM; Thompson, AD; Turle-Lorenzo, N, 2012)	0.38
"A short-term, randomized, partly blinded, crossover, investigator-initiated clinical trial was performed, with levodopa/carbidopa intestinal gel combined with oral entacapone and tolcapone on two different days in 10 patients."	( Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial. Askmark, H; Johansson, A; Lennernäs, H; Nyholm, D, 2012)	2.03
" However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia."	( Occlusion-amblyopia following high dose oral levodopa combined with part time patching. Kothari, M, 2014)	0.92
" However, our results suggest that mavoglurant combined with higher doses of L-dopa may be effective in treating patients with Parkinson's disease experiencing L-dopa-related motor fluctuations and dyskinesias."	( Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson's disease patients. Dronamraju, N; Graf, A; Hauser, RA; Kenney, C; Kumar, R; Merschhemke, M; Mostillo, J, 2016)	0.69
" The cost-effectiveness of DBS combined with BMT, versus BMT alone, was evaluated from a UK payer perspective."	( The cost-effectiveness of deep brain stimulation in combination with best medical therapy, versus best medical therapy alone, in advanced Parkinson's disease. Annoni, E; Ashkan, K; Chaudhuri, KR; Deuschl, G; Eggington, S; Valldeoriola, F, 2014)	0.4
"The aim of this review is to describe the rationale and main underlying reasons for undertaking, during clinical development, the study of drug candidates used separately and/or in combination with other technologies."	( Rationale for Assessing Safety and Efficacy of Drug Candidates Alone and in Combination with Medical Devices: The Case Study of SpinalonTM. Guertin, PA, 2017)	0.46
"To evaluate the effectiveness and safety of acupuncture combined with Madopar for the treatment of Parkinson's disease (PD), compared to the use of Madopar alone."	( Effectiveness and safety of acupuncture combined with Madopar for Parkinson's disease: a systematic review with meta-analysis. Chen, L; Chen, W; Dong, H; Geng, G; Li, T; Liu, H; Zhan, S; Zhang, Z, 2017)	0.46
" Meta-analyses showed that acupuncture combined with Madopar for the treatment of PD can significantly improve the clinical effectiveness compared with Madopar alone (RR=1."	( Effectiveness and safety of acupuncture combined with Madopar for Parkinson's disease: a systematic review with meta-analysis. Chen, L; Chen, W; Dong, H; Geng, G; Li, T; Liu, H; Zhan, S; Zhang, Z, 2017)	0.46
"Acupuncture combined with Madopar appears, to some extent, to improve clinical effectiveness and safety in the treatment of PD, compared with Madopar alone."	( Effectiveness and safety of acupuncture combined with Madopar for Parkinson's disease: a systematic review with meta-analysis. Chen, L; Chen, W; Dong, H; Geng, G; Li, T; Liu, H; Zhan, S; Zhang, Z, 2017)	0.46
" Dilution of propionic anhydride 1:4 (v/v) in acetonitrile in combination with 50 μL of plasma resulted in the highest mass spectrometric response."	( In Matrix Derivatization Combined with LC-MS/MS Results in Ultrasensitive Quantification of Plasma Free Metanephrines and Catecholamines. Bischoff, R; de Jong, WHA; Eijkelenkamp, K; Kema, IP; van der Ley, CP; van Faassen, M, 2020)	0.56
"In total, 160 PD patients who were admitted to our hospital were equally randomized into a control treatment group (levodopa alone) and the study group (pramipexole combined with levodopa)."	( Efficacy of pramipexole combined with levodopa for Parkinson's disease treatment and their effects on QOL and serum TNF- Ding, J; Hong, W; Huang, J; Ren, Y; Yang, Z, 2020)	1.04
"Pramipexole combined with levodopa relieved PD symptoms and improved the quality of life of PD patients, potentially by suppressing serum TNF-α levels."	( Efficacy of pramipexole combined with levodopa for Parkinson's disease treatment and their effects on QOL and serum TNF- Ding, J; Hong, W; Huang, J; Ren, Y; Yang, Z, 2020)	1.13
"To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use."	( [Systematic review and screening of basic Chinese herbs for traditional Chinese medicine compounds combined with levodopa medicine in treatment of Parkinson's disease]. He, TZ; Liu, DD; Liu, HJ; Tan, LJ; Wu, Q; Zhang, JL, 2020)	0.98
" The subjects in the control group received only levodopa and benserazide hydrochloride treatment, while the observation group was treated with Resagiline in combination with the clinical control group."	( Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson's disease. Gao, F; Gao, L; Miao, J; Yang, Y, 2023)	1.44
"In patients with Parkinson's disease who are in the middle and late stages of the disease, the administration of Resagiline combined with levodopa and benserazide hydrochloride can significantly lower the body's serum Hcy level, significantly raise IGF-1 levels, and significantly improve motor function in patients with Parkinson's disease."	( Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson's disease. Gao, F; Gao, L; Miao, J; Yang, Y, 2023)	1.39

Bioavailability

This study aimed to examine the effects of banana juice on levodopa bioavailability in rats. Domperidone slightly increases the immediate bioavailability (over 4 h) and anti-parkinsonian response to a given dose of Levodopa.

Excerpt	Reference	Relevance
" A number of these derivatives effectively prevent the metabolism of L-Dopa prior to and/or during the absorption process, resulting in a significantly better bioavailability of the drug."	( Improved delivery through biological membranes. 4. Prodrugs of L-dopa. Bodor, N; Higuchi, T; Sasahara, K; Sloan, KB, 1977)	0.26
"The physiological basis for the reduced levodopa bioavailability following oral administration was investigated."	( Influence of route of administration on physiological availability of levodopa in dogs. Boxenbaum, HG; Cotler, S; Holazo, A; Kaplan, SA, 1976)	0.76
" This non-linear increase in laevodopa bioavailability is consistent with the hypothesis that high oral doses of laevodopa are required to saturate gastro-intestinal metabolism of the drug."	( Dose-dependent pharmacokinetics of laevodopa and its metabolites in the rat. Cheng, LK; Fung, HL, 1976)	0.26
" There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa."	( Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease. Astarloa, R; de la Vega, L; de Yébenes, JG; Mena, MA; Sánchez, V, 1992)	0.28
" Almost equivalent bioavailability (85-90%) of levodopa was demonstrated for the controlled-release formulations relative to that of conventional Madopar capsules."	( Comparative multiple-dose pharmacokinetics of controlled-release levodopa products. Collin, C; Eckernäs, SA; Grahnén, A; Ling-Andersson, A; Nilsson, M; Tiger, G, 1992)	0.78
" Bioavailability of Sinemet CR levodopa is less than that of standard Sinemet, so a slightly higher total daily levodopa dose is required to achieve a comparable effect; but because Sinemet CR is absorbed much more slowly than is the standard preparation, dosing frequency can be reduced by up to half."	( The use of Sinemet CR in the management of mild to moderate Parkinson's disease. Rodnitzky, RL, 1992)	0.57
" A significant negative regression was also seen of duration of therapy on the dose absorbed per unit distribution volume, but not on the elimination rate constant, indicating a decrease in bioavailability and/or an increase in distribution volume with duration."	( Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease. Bowes, SG; Deshmukh, AA; Dobbs, RJ; Dobbs, SM; Leeman, AL; Nicholson, PW; O'Neill, CJ, 1991)	0.6
" The relative bioavailability of SL apomorphine ranged from 10 to 22% of a parenteral apomorphine dose."	( Absorption of apomorphine by various routes in parkinsonism. Gancher, ST; Nutt, JG; Woodward, WR, 1991)	0.28
" dosing (65 min), and bioavailability was 40%."	( Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary excretion of gamma-L-glutamyl-L-dopa in the rat. Cummings, J; Matheson, LM; Maurice, L; Smyth, JF, 1990)	0.28
"The effect of chronic intake of the anticholinergic drug orphenadrine on the bioavailability of levodopa was studied in six patients with Parkinson's disease."	( Combined levodopa-anticholinergic therapy in the treatment of Parkinson's disease. Effect on levodopa bioavailability. Albani, F; Baruzzi, A; Contin, M; Martinelli, P; Procaccianti, G; Riva, R, 1991)	0.92
" enhanced bioavailability and prolonged plasma half-life of L-DOPA, pronounced DOPA sparing effect and blockade of 3-OMD formation."	( Ro 40-7592: inhibition of COMT in rat brain and extracerebral tissues. Colzi, A; Da Prada, M; Zürcher, G, 1990)	0.28
" The methods have been utilized to evaluate the pharmacokinetics and bioavailability of oral dosage forms containing levodopa and carbidopa."	( Simultaneous high-performance liquid chromatographic analysis of carbidopa, levodopa and 3-O-methyldopa in plasma and carbidopa, levodopa and dopamine in urine using electrochemical detection. August, TF; Bayne, WF; Eisenhandler, R; Musson, DG; Titus, DC; Yeh, KC, 1990)	0.72
" The negative aspects of Madopar HBS are a lower bioavailability that means a dosage increase and a longer latency for the therapeutic response in the morning."	( Long-term treatment with Madopar HBS in parkinsonians with fluctuations. Aljanati, R; Buzó, R; Caamaño, JL; Chouza, C; De Medina, O; Fernandez, A; Plachín, V; Romero, S; Scaramelli, A, 1990)	0.28
" Nitecapone slightly but significantly increased the relative bioavailability of L-Dopa."	( Effect of a novel catechol-O-methyltransferase inhibitor, nitecapone, on the metabolism of L-dopa in healthy volunteers. Gordin, A; Järvinen, M; Kaakkola, S; Nissinen, E; Pentikäinen, PJ; Rita, H; Schultz, E; Wikberg, T, 1990)	0.28
" This study examined the effects of administering ferrous sulphate 325 mg with Sinemet (100/25 tablet) on levodopa and carbidopa bioavailability and on signs of Parkinson's disease in nine patients."	( Sinemet-ferrous sulphate interaction in patients with Parkinson's disease. Campbell, NR; Goodridge, AE; Hasinoff, BB; Kara, M; Rankine, D, 1990)	0.49
"Ferrous sulfate decreases L-dopa bioavailability in humans probably as a result of binding of L-dopa by iron in the gastrointestinal tract."	( The effect of ferrous sulfate and pH on L-dopa absorption. Barrowman, J; Campbell, NR; Campbell, RR; Chernenko, G; Hasinoff, B, 1990)	0.28
" Mean levodopa plasma levels were comparable between the two types of formulations during optimal treatment, however systemic bioavailability was significantly higher with CR-4."	( Clinical and pharmacokinetic evaluation of controlled-release levodopa/carbidopa (CR-4) in parkinsonian patients with severe motor fluctuations: a six month follow-up study. Deleu, D; Ebinger, G; Jacques, M; Michotte, Y, 1989)	1
" Current research is directed at overcoming this effect by 1) combining levodopa with new dopamine agonists such as cabergoline or terguride, which have useful pharmacological properties; 2) administering the drugs in different ways to improve their bioavailability (intravenous or subcutaneous infusion); 3) understanding the neurobiological implications of cellular brain grafting; 4) safely transferring the surgical procedure from the experimental to the clinical field."	( [Current approaches in the treatment of Parkinson disease]. Caraceni, T; Geminiani, G; Tamma, F, 1989)	0.51
" Total daily levodopa intake was greater with Sinemet CR, although the bioavailability of levodopa and carbidopa from the two preparations was equivalent."	( A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100). Cedarbaum, JM; Kutt, H; McDowell, FH, 1989)	0.65
"Prodrugs may be used to improve the absorption and bioavailability of certain active compounds."	( NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. Iversen, SD; Miyaji, M; Naruse, T; Rupniak, NM; Tye, SJ, 1989)	0.28
" Total daily levodopa dosage increased from 623 to 808 mg/day (+33%), a factor consistent with the lower bioavailability of the controlled-release formulation."	( An open multicenter long-term treatment evaluation of Sinemet CR. Sinemet CR Multicenter Study Group. Bush, DF; Liss, CL; Morton, A, 1989)	0.65
" Results indicate a levodopa bioavailability of 71% for Sinemet CR, in contrast to a bioavailability of 99% for Sinemet for these subjects."	( Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. August, TF; Bush, DF; Lasseter, KC; Musson, DG; Schwartz, S; Smith, ME; Titus, DC; Yeh, KC, 1989)	0.6
" Levodopa bioavailability and clearance were similar between formulations."	( Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. Berchou, RC; Galloway, MP; Kareti, D; Kesaree, N; LeWitt, PA; Nelson, MV; Schlick, P, 1989)	1.48
" Although dosages of CR required for an optimal therapeutic response were not significantly higher compared with conventional levodopa, bioavailability significantly increased."	( Controlled-release carbidopa/levodopa (CR) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations. Deleu, D; Ebinger, G; Jacques, M; Michotte, Y, 1989)	0.77
"5-fold increase in daily carbidopa intake on the bioavailability of levodopa was studied in six patients with Parkinson's disease on a low chronic regimen of carbidopa-levodopa (Sinemet) at the fixed ratio of 1:10."	( Increased dosage of carbidopa in parkinsonian patients on low carbidopa-levodopa regimen. Effect on levodopa bioavailability. Baruzzi, A; Contin, M; Martinelli, P; Procaccianti, G; Riva, R, 1989)	0.74
"The bioavailability of L-dopa following rectal administration of a series of short-chain alkyl esters of L-dopa was determined in rats and dogs."	( Short-chain alkyl esters of L-dopa as prodrugs for rectal absorption. Alexander, J; Cortese, M; Engle, K; Fix, JA; Leppert, P; Repta, AJ, 1989)	0.28
" The bioavailability of levodopa was significantly greater in the elderly (0."	( The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. Everest, H; George, CF; Monks, K; Renwick, AG; Robertson, DR; Waller, DG; Wood, ND, 1989)	0.84
"4 times larger bioavailability (AUC) on plasma L-dopa concentrations than those of L-dopa itself."	( A new potential prodrug to improve the duration of L-dopa: L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine. Hisaka, A; Ihara, M; Sawasaki, Y; Takehana, H; Tomimoto, K; Tsuchiya, Y; Yano, M, 1989)	0.28
" Current research efforts are directed at developing oral dopamine analogs that exhibit improved bioavailability and do not traverse the blood-brain barrier."	( The use of levodopa, an oral dopamine precursor, in congestive heart failure. Broderick, G; Rajfer, SI, 1989)	0.67
"This study examined the effect of ferrous sulfate, a widely used iron treatment, on levodopa bioavailability in normal subjects."	( Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism. Campbell, NR; Hasinoff, B, 1989)	0.81
"The effect of doubling carbidopa intake on single dose bioavailability of L-Dopa was examined in five parkinsonian patients."	( Effect of supplemental carbidopa on bioavailability of L-dopa. Cedarbaum, JM; Dhar, AK; Kutt, H; McDowell, FH; Watkins, S, 1986)	0.27
"The bioavailability of levodopa-benserazide in a standard capsule and a new dispersible tablet was compared in Parkinsonian patients, with (n = 8) and without (n = 8) swallowing difficulties."	( Bioavailability and acceptability of a dispersible formulation of levodopa-benserazide in parkinsonian patients with and without dysphagia. Bayer, AJ; Day, JJ; Finucane, P; Pathy, MS, 1988)	0.82
" The clinical response to Madopar HBS was delayed and brief; the relative bioavailability was only 50%."	( Single-dose studies of a slow-release preparation of levodopa and benserazide (Madopar HBS) in Parkinson's disease. Jenner, P; Malcolm, SL; Marion, MH; Marsden, CD; Quinn, NP; Stocchi, F, 1987)	0.52
" As compared with Sinemet CR4, there was a greater delay in the occurrence of peak plasma levodopa concentrations, and relative bioavailability was reduced."	( Controlled-release levodopa/carbidopa. III: Sinemet CR5 treatment of response fluctuations in Parkinson's disease. Cedarbaum, JM; Hoey, M; Kutt, H; McDowell, FH, 1988)	0.82
" In comparison with standard Madopar the rate of absorption is reduced, providing lower peak concentrations of L-dopa."	( Single-dose pharmacokinetics of Madopar HBS in patients and effect of food and antacid on the absorption of Madopar HBS in volunteers. Allen, JG; Bird, H; Malcolm, SL; Marion, MH; Marsden, CD; O'Leary, CG; Quinn, NP, 1987)	0.27
" The mean relative bioavailability (versus standard Madopar) was 58 and 67% (value normalized to dose) for one and two HBS capsules, respectively."	( Bioavailability of L-dopa after Madopar HBS administration in healthy volunteers. Crevoisier, C; Da Prada, M; Hoevels, B; Zürcher, G, 1987)	0.27
" In nine subjects who completed the trial, the clinical response, occurrence of dyskinesias and of nausea and vomiting, were similar with both treatments, although peak plasma levodopa concentration and levodopa bioavailability were greater on levodopa-domperidone than on levodopa-carbidopa."	( Comparison of levodopa with carbidopa, and levodopa with domperidone in Parkinson's disease. Langdon, N; Malcolm, PN; Parkes, JD, 1986)	0.82
" However, response fluctuations continued to occur, day-to-day consistency was poor, and the bioavailability of levodopa appeared less than that of standard Sinemet."	( Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease. Breck, L; Cedarbaum, JM; Kutt, H; McDowell, FH, 1987)	0.81
" Using this value for clearance, it is estimated that carbidopa doubles the bioavailability of orally administered levodopa."	( The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: the mechanism of action in the treatment of parkinsonism. Anderson, JL; Nutt, JG; Woodward, WR, 1985)	0.71
" This tablet was considered appropriate for the bioavailability tests described in this paper."	( Dosage form design for improvement of bioavailability of levodopa VI: formulation of effervescent enteric-coated tablets. Arai, M; Ikegami, Y; Morioka, T; Nakajima, E; Nishimura, K; Nitanai, T; Sasahara, K, 1984)	0.51
" 163, administered as their DL-racemic mixtures, produced increases in the t1/2 and bioavailability of co-administered L-DOPA comparable to that produced by a 10-fold larger dose of carbidopa administered as the active L-enantiomer; increasing the dose of MDL 72."	( A comparison of the effects of reversible and irreversible inhibitors of aromatic L-amino acid decarboxylase on the half-life and other pharmacokinetic parameters of oral L-3,4-dihydroxyphenylalanine. Haegele, KD; Huebert, ND; Palfreyman, MG, )	0.13
"To investigate the relation between "on-off" fluctuations in symptomatology and bioavailability of dopa in patients with Parkinson's disease, five Parkinsonian patients with pronounced "on-off" symptoms were studied."	( "On-off" phenomenon in Parkinson's disease: correlation to the concentration of dopa in plasma. Carlsson, A; Eriksson, T; Granérus, AK; Linde, A; Magnusson, T, 1984)	0.27
" Domperidone slightly increases the immediate bioavailability (over 4 h) and anti-parkinsonian response to a given dose of levodopa."	( Domperidone and levodopa in Parkinson's disease. Davies, CL; Dolan, AL; Finnerty, GT; Parkes, JD; Shindler, JS; Towlson, K, 1984)	0.82
"Various drugs have been studied in order to improve the bioavailability of L-DOPA."	( Effects of 3,4-dihydroxyphenylpyruvic acid and its triacetylated derivative on DOPA decarboxylase. Lindén, IB; Neuvonen, PJ; Vapaatalo, H, 1982)	0.26
"Several potential mechanisms for reduced levodopa bioavailability following oral administration to dogs and humans were investigated by studying the influence of the administration route on plasma levodopa levels after intravenous, hepatoportal, and duodenal administrations to dogs."	( Dosage form design for improvement of bioavailability of levodopa IV: Possible causes of low bioavailability of oral levodopa in dogs. Habara, T; Kawahara, Y; Kojima, T; Morioka, T; Nakajima, E; Nitanai, T; Sasahara, K, 1981)	0.77
"To estimate the absolute bioavailability of oral levodopa, plasma concentrations and urinary excretion of levodopa and its metabolites were determined in beagle dogs and in parkinsonian patients after intravenous and oral drug administration."	( Dosage form design for improvement of bioavailability of levodopa II: bioavailability of marketed levodopa preparations in dogs and parkinsonian patients. Habara, T; Morioka, T; Nakajima, E; Nitanai, T; Sasahara, K, 1980)	0.76
" The mean bioavailability varied between 14."	( Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: a study of five different suppositories. Danhof, M; Jansen, EN; Neef, C; Roos, RA; van Laar, T, 1995)	0.29
" There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar."	( Lack of an effect of Madopar on the disposition of tolcapone and its 3-O-methylated metabolite in rats. Fukazawa, H; Funaki, T; Kuruma, I; Onodera, H; Tagami, C; Tsukamoto, Y; Ushiyama, N, 1995)	0.29
" These findings support the notion that tolcapone has the ability to enhance striatal dopamine neurotransmission by increasing L-dopa bioavailability through peripheral and central inhibition of L-dopa O-methylation, as well as by blocking the central conversion of dopamine into 3-methoxytyramine."	( Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal metabolism of L-dopa and dopamine in rats. Da Prada, M; Napolitano, A; Zürcher, G, 1995)	0.29
" In animal studies, these compounds inhibit effectively the O-methylation of L-dopa, thus improving its bioavailability and brain penetration and potentiating its behavioural effects."	( General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase. Gordin, A; Kaakkola, S; Männistö, PT, 1994)	0.29
" The compounds examined ranged from well- to poorly-absorbed and included compounds absorbed by active and passive mechanisms."	( Use of everted intestinal rings for in vitro examination of oral absorption potential. Fix, JA; Leppert, PS, 1994)	0.29
" There was a significantly higher extent and slower rate of absorption when levodopa was administered ip in a large volume of vehicle."	( Pharmacokinetics of levodopa and carbidopa in rats following different routes of administration. Bredberg, E; Lennernäs, H; Paalzow, L, 1994)	0.84
"Catechol-O-methyltransferase (COMT) inhibitors may be useful in the treatment of Parkinson's disease by improving the bioavailability of levodopa and by prolonging its effects."	( Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson's disease. Bovingdon, M; Gordin, A; Lees, AJ; Merello, M; Webster, R, 1994)	0.7
" The relative bioavailability of levodopa in the solid preparation compared to the dispersion was in all patients 100%."	( Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson's disease. Aquilonius, SM; Bredberg, E; Johansson, K; Johnels, B; Nilsson, D; Nyström, C; Paalzow, L, 1993)	0.83
"We studied the effect of entacapone, a selective catechol-O-methyltransferase inhibitor, on the bioavailability and clinical effect of levodopa in Parkinson's disease (PD)."	( Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patients. Ahtila, S; Gordin, A; Kaakkola, S; Rita, H; Teräväinen, H, 1994)	0.73
" The L-DOPA was shown to hinder the absorption rate of glucose, whereas sulpiridinum was shown to suppress the main enzymes excepting snerase and alkaline phosphatase, to increase the monomeric and hydrolysate glucose transport."	( [The role of dopamine in the mechanism of the regulation of the digestive-transport functions of the enterocyte membrane during stress]. Guska, NI; Razlovan, TA; Sheptitskiĭ, VA, 1993)	0.29
" Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy."	( [Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease]. Eichhorn, TE; Kohnen, R; Oertel, WH; Poewe, W; Schrag, A; Selzer, R; Trenkwalder, C, 1995)	0.29
" Peripheral COMT inhibition with entacapone increased significantly the bioavailability of levodopa and prolonged its antiparkinsonian effect after a single dose and after repeated dosing for 4 weeks."	( Effect of one month's treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Rinne, UK; Ruottinen, HM, 1996)	0.71
" The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100 mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa."	( Sustained-release of levodopa: single dose study of a new formulation. Gerlach, M; Klotz, P; Kuhn, W; Müller, T; Przuntek, H, 1996)	0.89
" On the contrary, the [3H]mazindol tracer dose induced a marked labelling of the noradrenaline uptake complex in cerebellum; its prevention by desipramine (5 mg/kg) increased simultaneously the cerebral bioavailability and thereby the striatal labelling of the dopamine transporter."	( Pharmacological modifications of dopamine transmission do not influence the striatal in vivo binding of [3H]mazindol or [3H]cocaine in mice. Bonnet, JJ; Costentin, J; Thibaut, F; Vaugeois, JM, 1996)	0.29
" The lead compound SDZ EAB 515 was found to inhibit L-phenylalanine uptake by the large neutral amino acid carrier in vitro and in vivo; active transport may thus confer a good bioavailability to this class of compounds."	( Biphenyl-derivatives of 2-amino-7-phosphono-heptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonists--II. Pharmacological characterization in vivo. Campbell, E; Fricker, G; Jenner, P; Lemaire, M; McAllister, KH; Müller, W; Neijt, HC; Park, CK; Perkins, M; Rudin, M; Sauter, A; Smith, L; Urwyler, S; Wiederhold, KH, 1996)	0.29
" Aim of this open prospective study was to investigate (1) the efficacy of a new developed, parenteral application form of NADH on Parkinsonian symptoms and (2) the influence of bioavailability of levodopa."	( Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis. Danielczik, S; Gerstner, A; Häcker, R; Kuhn, W; Mattern, C; Müller, T; Przuntek, H; Winkel, R, 1996)	0.69
"The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon)."	( Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease. Hattori, Y; Kanazawa, I; Kowa, H; Kuno, S; Mizuno, Y; Narabayashi, H; Tohgi, H; Tsukamoto, Y; Yamamoto, M; Yanagisawa, N; Yokochi, M, 1997)	0.72
" Tolcapone had similar effects on plasma levodopa concentrations with the standard-release formulations: half-life and bioavailability increased approximately 2-fold compared with placebo, and maximum plasma concentration (Cmax) and time to Cmax (tmax) were unaffected, except for a slight increase in Cmax with the levodopa/benserazide 200/ 50 mg formulation."	( The effect of COMT inhibition by tolcapone on tolerability and pharmacokinetics of different levodopa/benserazide formulations. Aitken, J; Fotteler, B; Jorga, K; Nielsen, T; Schmitt, M; Zürcher, G, 1997)	0.78
" The absorption and bioavailability of CR 25/100 are minimally greater than CR 50/200."	( Controlled release levodopa/carbidopa 25/100 (Sinemet CR 25/100): pharmacokinetics and clinical efficacy in untreated parkinsonian patients. Block, GA; Cyhan, G; Gancher, ST; Hammerstad, JP; Nutt, JG; Woodward, WR, 1994)	0.62
" Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa."	( Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients. Baas, H; Beiske, AG; Ghika, J; Jackson, M; Oertel, WH; Poewe, W; Ransmayr, G, 1997)	0.74
" The total daily levodopa intake was significantly greater with L-CR because of the reduced bioavailability of the L-CR."	( Comparison of standard carbidopa-levodopa and sustained-release carbidopa-levodopa in Parkinson's disease: pharmacokinetic and quality-of-life measures. Koller, WC; Lyons, K; McGuire, D; Pahwa, R; Robischon, M; Silverstein, P; Zwiebel, F, 1997)	0.92
" Since this occurred following direct administration of l-DOPA into the striatum, the decrease could not be accounted for by peripheral pharmacodynamics or bioavailability of l-DOPA in the striatum."	( Effects of repeated administration of l-DOPA and apomorphine on circling behavior and striatal dopamine formation. Brannan, T; Prikhojan, A; Yahr, MD, 1998)	0.3
"Clinical pharmacology studies have shown that the catechol-O-methyltransferase inhibitor tolcapone increases the bioavailability area under the plasma concentration-time curve (AUC) and the plasma elimination half-life (t1/2) of levodopa."	( The effect of tolcapone on levodopa pharmacokinetics is independent of levodopa/carbidopa formulation. Aitken, J; Fotteler, B; Jorga, K; Nielsen, T; Sedek, G, 1998)	0.78
" With COMT inhibition, greater peripheral bioavailability of levodopa occurs in humans without an enhancement of peak plasma levels."	( Influence of COMT inhibition on levodopa pharmacology and therapy. Goetz, CG, 1998)	0.83
" When given together with levodopa/DCI, tolcapone increases the relative bioavailability and plasma elimination half-life of levodopa, without affecting its peak plasma concentration."	( Pharmacokinetics, pharmacodynamics, and tolerability of tolcapone: a review of early studies in volunteers. Jorga, KM, 1998)	0.6
" Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa."	( Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients. Baas, H; Beiske, AG; Ghika, J; Jackson, M; Oertel, WH; Poewe, W; Ransmayr, G, 1998)	0.74
" The bioavailability was significantly increased by 40% (AUC0-infinity=6."	( Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy subjects. Crevoisier, C; Dingemanse, J; Gasser, UE; Lankhaar, G; Ouwerkerk, M, 1998)	0.54
"Positron emission tomography (PET) seems to be a valuable method for the understanding of intestinal absorption mechanisms, for simultaneous quantitation of absorption rate and distribution kinetics to the tissues of interest after oral drug delivery."	( Absorption of L-DOPA from the proximal small intestine studied in the rhesus monkey by positron emission tomography. Aquilonius, SM; Fasth, KJ; Hartvig, P; Långström, B; Lennernäs, H; Nilsson, D; Sundin, A; Tedroff, J, 1999)	0.3
" Tolcapone increased the bioavailability (AUC 0-infinity) and apparent elimination half-life (t(1/2)) of levodopa by 80 and 40%, respectively, compared to placebo."	( COMT inhibition by tolcapone further improves levodopa pharmacokinetics when combined with a dual-release formulation of levodopa/benserazide. A novel principle in the treatment of Parkinson's disease. Crevoisier, C; Gasser, UE; Hovens, SE; Jorga, K; van Giersbergen, PL, 1999)	0.78
" The bioavailability of oral L-DOPA appears to vary with the dose."	( Renal effects of L-DOPA in heart failure. Goldstein, DS; Grossman, E; Peleg, E; Shenkar, A; Thaler, M, 1999)	0.3
" The absorption of the drug was shown to be rapid and concomitant food intake had only a minor effect on the relative bioavailability (10-20% reduction compared with fasting)."	( Population pharmacokinetics of tolcapone in parkinsonian patients in dose finding studies. Banken, L; Fotteler, B; Jorga, K; Snell, P; Steimer, JL, 2000)	0.31
" It has been shown to improve the bioavailability of plasma levodopa and extend its clinical effect when used as an adjunct to standard levodopa preparations, but there is little experience of the effect of entacapone on controlled release levodopa preparations."	( The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease. Brooks, DJ; Gordin, A; Karlsson, M; Korpela, K; Pavese, N; Piccini, P, 2000)	0.55
"A reliable multi-dimensional column chromatographic method employing amperometric detection using a carbon fibre microelectrode procedure was used for monitoring the plasma profiles and to evaluate the pharmacokinetics and bioavailability of levodopa (L-dopa) and carbidopa (C-dopa), after ingestion of oral formulations containing these drugs."	( Bioavailability studies of oral dosage forms containing levodopa and carbidopa using column-switching chromatography followed by electrochemical detection. Sagar, KA; Smyth, MR, 2000)	0.74
" The consequent increase in levodopa bioavailability was mostly offset by reductions in levodopa dose."	( Population pharmacokinetics of levodopa in patients with Parkinson's disease treated with tolcapone. Banken, L; Fotteler, B; Jorga, K; Snell, P; Steimer, JL, 2000)	0.89
" In human volunteers, both entacapone and tolcapone dose-dependently inhibit the COMT activity in erythrocytes, improve the bioavailability and decrease the elimination of levodopa, and inhibit the formation of 3-O-methyldopa (3-OMD)."	( Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Kaakkola, S, 2000)	0.5
" Absorption was fast following nasal delivery of the prodrugs with bioavailability around 90%."	( Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs. Dittert, L; Hussain, A; Itoh, S; Kao, HD; Traboulsi, A, 2000)	0.31
" In the simulated studies, up to half of the study subjects exhibited FCM, and various levels of intrasubject variability were incorporated into the absorption rate constant."	( First measured plasma concentration value as C(max); impact on the C(max) confidence interval in bioequivalence studies. Conner, D; Jackson, A; Miller, R, 2000)	0.31
" Results indicate that the first-ever dose of oral L-Dopa is well absorbed and that pharmacokinetic mechanisms such as reduced absorption of L-Dopa probably do not play a major role in the initial delay in clinical response to oral L-Dopa/carbidopa in patients with Parkinson's disease."	( The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo patients with Parkinson's disease. Djaldetti, R; Melamed, E; Rosmarin, V; Ziv, I, )	0.37
" In addition, the choice of alternate formulations and routes of administration will not only improve on the bioavailability and overall pharmacokinetics of levodopa, but also increase compliance."	( Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa. Okereke, CS, )	0.52
" The relative bioavailability (Madopar DR vs."	( Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy volunteers. Crevoisier, C; Metzger, B; Monreal, A; Nilsen, T, 2003)	0.56
" The absolute bioavailability of cabergoline is unknown."	( Clinical pharmacokinetics of cabergoline. Bonuccelli, U; Del Dotto, P, 2003)	0.32
"Novel glycosyl derivatives of dopamine and L-dopa (I-IV) are synthesized in order to overcome the problem of blood-brain barrier low permeability of dopamine and of low bioavailability of its precursor L-dopa."	( Glycosyl derivatives of dopamine and L-dopa as anti-Parkinson prodrugs: synthesis, pharmacological activity and in vitro stability studies. Boatto, G; Bonina, F; Calignano, A; De Caprariis, P; La Rana, G; Melisi, D; Nieddu, M; Puglia, C; Rimoli, MG, 2003)	0.32
"There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities."	( [Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study]. Chaná, P; Fierro, A; Reyes-Parada, M; Sáez-Briones, P, 2003)	0.57
" In conclusion, the novel COMT inhibitor BIA 3-202 was well tolerated and significantly increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard release levodopa/benserazide."	( Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/benserazide. Almeida, L; Falcão, A; Loureiro, A; Machado, R; Maia, J; Silveira, P; Soares-da-Silva, P; Torrão, L; Vaz-da-Silva, M; Wright, L, 2003)	0.75
" In switching patients who are receiving levodopa/carbidopa controlled-release (CR), it should be noted that the bioavailability of levodopa from levodopa/carbidopa CR is approximately 70-75% that of levodopa/carbidopa IR products, including Stalevo."	( Levodopa/carbidopa/entacapone (Stalevo). Hauser, RA, 2004)	2.03
" This increased duration of 'on' time was concomitant with a significant increase in levodopa bioavailability (AUC)."	( Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients. Barbato, L; Bolner, A; Caraceni, T; Nordera, G; Stocchi, F, 2004)	0.77
" In conclusion, the novel COMT inhibitor BIA 3-202 increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard levodopa/carbidopa."	( Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/carbidopa. Almeida, L; Falcão, A; Loureiro, A; Machado, R; Maia, J; Silveira, P; Soares-da-Silva, P; Torrão, L; Vaz-da-Silva, M; Wright, L, )	0.58
" Long-term levodopa administration results in an increased levodopa plasma bioavailability in PD patients."	( Chronic levodopa intake increases levodopa plasma bioavailability in patients with Parkinson's disease. Muhlack, S; Müller, T; Przuntek, H; Twiehaus, S; Welnic, J; Woitalla, D, 2004)	1.15
" COMT inhibitors prolong the elimination of LD, while DDC inhibitors mainly increase its absorption; both mechanisms leading to increased bioavailability of LD."	( Clinical advantages of COMT inhibition with entacapone - a review. Gordin, A; Kaakkola, S; Teräväinen, H, 2004)	0.32
"Entacapone is a COMT inhibitor used in Parkinson's disease (PD) patients, as an adjunctive therapy to L-dopa in order to prolong its bioavailability and thus its clinical effect."	( Delayed administration may improve entacapone effects in parkinsonian patients non-responding to the drug. Bassi, A; Brusa, L; Fedele, E; Lunardi, G; Pasqualetti, P; Peppe, A; Pierantozzi, M; Stanzione, P; Stefani, A, 2004)	0.32
" To improve the bioavailability of the synthesized prodrugs, they were encapsulated in unilamellar liposomes of dimiristoylphosphatidylcholine (DMPC) and cholesterol (CHOL)."	( Evaluation of rat striatal L-dopa and DA concentration after intraperitoneal administration of L-dopa prodrugs in liposomal formulations. Braghiroli, D; Cannazza, G; Carafa, M; Di Stefano, A; Marianecci, C; Orlando, G; Pinnen, F; Ricciutelli, M; Santucci, E; Sozio, P, 2004)	0.32
" When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron."	( [Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs]. Kamimura, N; Murayama, N; Sunagane, N; Terawaki, Y; Uruno, T; Yoshinobu, E, 2005)	0.76
" Catechol-O-methyltransferase (COMT) inhibitors increase the half-life and bioavailability of levodopa, providing more continuous dopamine receptor stimulation."	( Early administration of entacapone prevents levodopa-induced motor fluctuations in hemiparkinsonian rats. Aguilar, E; Bonastre, M; Marin, C; Obeso, JA; Tolosa, E, 2005)	0.81
" The use of catechol-O-methyl transferase (COMT) inhibitors likewise increases the bioavailability and brings about a smooth drug profile."	( A walk through the management of Parkinson s disease. Lim, E, 2005)	0.33
" Entacapone increases the bioavailability and reduces the daily variation of plasma levodopa when administered with standard levodopa preparations."	( Entacapone increases levodopa exposure and reduces plasma levodopa variability when used with Sinemet CR. Gordin, A; Huupponen, R; Kultalahti, ER; Laine, K; Leinonen, M; Paija, O; Reinikainen, K, )	0.67
" In this experimental study we have investigated whether the presence of Plantago ovata husk (water-soluble fiber) modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route at the same time."	( Hydrosoluble fiber (Plantago ovata husk) and levodopa I: experimental study of the pharmacokinetic interaction. Calle, A; Carriedo, D; Diez, MJ; Fernandez, N; Garcia, JJ; Gonzalez, A; Sahagun, A; Sierra, M, 2005)	0.78
" ovata husk modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route with carbidopa (5 mg/kg)."	( Hydrosoluble fiber (Plantago ovata husk) and levodopa II: experimental study of the pharmacokinetic interaction in the presence of carbidopa. Calle, A; Carriedo, D; Diez, MJ; Fernandez, N; Garcia, JJ; Gonzalez, A; Sahagun, A; Sierra, M, 2005)	0.81
"This study aimed to examine the effects of banana juice on levodopa bioavailability in rats."	( Banana juice reduces bioavailability of levodopa preparation. Ogo, Y; Ohta, T; Sunagane, N; Uruno, T, 2005)	0.84
" On this pretense, attempts to reduce the bioavailability of melatonin using a melatonin receptor antagonist have been found to completely restore behavioral and regulatory function in the presence of chronically reduced levels of dopamine, without producing side effects commonly seen with traditional dopamine replacement therapy."	( The role of ML-23 and other melatonin analogues in the treatment and management of Parkinson's disease. Willis, GL, 2005)	0.33
" The study on levodopa bioavailability showed 3-4 times differences in individual patients."	( [Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease]. Moritoyo, H; Moritoyo, T; Nagai, M; Nakatsuka, A; Nisikawa, N; Nomoto, M; Yabe, H, 2005)	0.69
" These findings demonstrate that endogenous melatonin protects exogenous L-DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co-administration of melatonin with L-DOPA markedly increases striatal L-DOPA bioavailability in control as well as in melatonin-depleted rats."	( Endogenous melatonin protects L-DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L-DOPA therapy in Parkinson's disease. Desole, MS; Esposito, G; Marchetti, B; Miele, E; Migheli, R; Rocchitta, G; Serra, PA, 2006)	0.33
" Individual differences in the central bioavailability of L-DOPA may provide a clue to the varying susceptibility to dyskinesia in Parkinson's disease."	( Role of striatal L-DOPA in the production of dyskinesia in 6-hydroxydopamine lesioned rats. Carta, M; Cenci, MA; Fadda, F; Lindgren, HS; Lundblad, M; Stancampiano, R, 2006)	0.33
" These results indicate that there may be some interactions between the levodopa preparation and these OTC kampo medicines when ingested together, which leads to a reduction in the bioavailability of levodopa."	( [Possibility of interactions between prescription drugs and OTC drugs (2nd report)--interaction between levodopa preparation and OTC Kampo medicines for upset stomach]. Aikawa, M; Ohta, T; Sunagane, N; Uruno, T, 2006)	0.78
"The maleic and fumaric diamides preparation of (O,O-diacetyl)-L-Dopa-methylester [(+)-4, (+)-5] are reported; they were synthesized in order to attenuate marked fluctuations of L-DOPA (LD) plasma levels and to overcome the problem of low bioavailability of LD."	( Maleic- and fumaric-diamides of (O,O-diacetyl)-L-Dopa-methylester as anti-Parkinson prodrugs in liposomal formulation. Carafa, M; Di Stefano, A; Iannitelli, A; Marianecci, C; Santucci, E; Sozio, P, 2006)	0.33
" Monoamine oxidase type B (MAO-B) inhibitors can be used across the spectrum of disease severity, but selegiline (deprenyl), the prototype in this class, is characterised by low and erratic bioavailability of the parent drug and conversion to amphetamine metabolites that may increase the risk of adverse events."	( Community and long-term care management of Parkinson's disease in the elderly: focus on monoamine oxidase type B inhibitors. Chen, JJ; Fernandez, HH, 2007)	0.34
" The oral disintegrating tablet formulation of selegiline allows pregastric absorption, minimizing first-pass metabolism, thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites."	( Monoamine oxidase-B inhibition in the treatment of Parkinson's disease. Chen, JJ; Fernandez, HH, 2007)	0.34
"Methods for facilitation of pyloric passage or increase of bioavailability are discussed."	( Irregular gastrointestinal drug absorption in Parkinson's disease. Lennernäs, H; Nyholm, D, 2008)	0.35
" The main factors responsible for the poor bioavailability and the wide range of inter- and intra-patient variations of plasma levels are the drug's physical-chemical properties: low water and lipid solubility, resulting in unfavourable partition, and the high susceptibility to chemical and enzymatic degradation."	( Antiparkinson prodrugs. Cerasa, LS; Di Stefano, A; Sozio, P, 2008)	0.35
"The influence of treatment duration (7 or 14 days) with Plantago ovata husk/levodopa/carbidopa in the bioavailability and other pharmacokinetic parameters of levodopa were evaluated in rabbits."	( The hydrosoluble fiber Plantago ovata husk improves levodopa (with carbidopa) bioavailability after repeated administration. Diez, MJ; Fernandez, N; Garcia, JJ; Prieto, C; Sahagun, A; Sierra, M, 2008)	0.83
" Entacapone inhibits the metabolism of levodopa therefore increases the area under the plasma concentration-time profile of levodopa; however, it may decrease the initial absorption rate of levodopa in some patients probably due to competitive absorption."	( The pharmacokinetics and pharmacodynamics of levodopa in the treatment of Parkinson's disease. Hsu, A; Khor, SP, 2007)	0.87
"The aim of the study was to explore the potential effect of the catechol-O-methyltransferase inhibitor entacapone coadministration on the rate of absorption and matched latency to motor response of an oral test dose of levodopa/benserazide in the treatment of Parkinson disease (PD)."	( The effect of entacapone on levodopa rate of absorption and latency to motor response in patients with Parkinson disease. Albani, F; Avoni, P; Baruzzi, A; Contin, M; Martinelli, P; Riva, R; Scaglione, C, )	0.61
"Slow gastric emptying decreasing levodopa (LD) bioavailability contributes to motor fluctuations in Parkinson disease (PD)."	( Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study. Antonini, A; Guidi, M; Mancini, F; Martignoni, E; Pacchetti, C; Sciarretta, M; Stocchi, F; Zangaglia, R, )	0.71
"Antibiotic therapy to eradicate Helicobacter pylori, the causative agent of gastric and duodenal ulcers, has been suggested to improve L-DOPA bioavailability in Parkinson's and thereby improve patient symptomology."	( Microbial endocrinology as a basis for improved L-DOPA bioavailability in Parkinson's patients treated for Helicobacter pylori. Lyte, M, 2010)	0.36
" However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels."	( Levodopa delivery systems: advancements in delivery of the gold standard. Choonara, Y; Du Toit, LC; Modi, G; Naidoo, D; Ndesendo, V; Ngwuluka, N; Pillay, V, 2010)	1.8
"The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated."	( Levodopa delivery systems: advancements in delivery of the gold standard. Choonara, Y; Du Toit, LC; Modi, G; Naidoo, D; Ndesendo, V; Ngwuluka, N; Pillay, V, 2010)	1.8
" With the aim to increase the bioavailability after oral administration, we designed a multi-protected L-DOPA prodrugs able to release the drug by both spontaneous chemical or enzyme catalyzed hydrolysis."	( Design, synthesis, and preliminary pharmacological evaluation of new imidazolinones as L-DOPA prodrugs. Cerasa, LS; Chiavaroli, A; Claudi, F; Di Stefano, A; Ferrante, C; Giorgioni, G; Glennon, RA; Orlando, G; Palmieri, GF; Ricciutelli, M; Ruggieri, S; Sozio, P, 2010)	0.36
" One time addition of EN to LD/CD showed no increase of maximum LD concentration, but repeat EN supplementation to LD/CD elevated LD bioavailability and peaks."	( Entacapone. Müller, T, 2010)	0.36
"The absorption rate was significantly delayed at nighttime dosing."	( Circadian rhythmicity in levodopa pharmacokinetics in patients with Parkinson disease. Aquilonius, SM; Estrada, M; Johansson, A; Lennernäs, H; Nyholm, D, 2010)	0.66
"There is a slower absorption rate of levodopa during nighttime, probably related to delayed gastric emptying."	( Circadian rhythmicity in levodopa pharmacokinetics in patients with Parkinson disease. Aquilonius, SM; Estrada, M; Johansson, A; Lennernäs, H; Nyholm, D, 2010)	0.94
" Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry."	( Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies. Bishop, SC; Fukui, M; Kang, KS; Wen, Y; Yamabe, N; Zhu, BT, 2010)	0.6
" The oral bioavailability of D-phenylglycine-L-dopa was 31."	( Evidence of D-phenylglycine as delivering tool for improving L-dopa absorption. Fan, YB; Lu, HH; Tsai, MC; Tsai, TH; Wang, CL; Wang, HP, 2010)	0.36
" The higher jejunal permeability and the improved systemic bioavailability of D-phenylglycine-L-dopa in comparison to that of l-dopa suggested that D-phenylglycine is an effective delivery tool for improving the oral absorption of drugs like L-dopa with unsatisfactory pharmacokinetics."	( Evidence of D-phenylglycine as delivering tool for improving L-dopa absorption. Fan, YB; Lu, HH; Tsai, MC; Tsai, TH; Wang, CL; Wang, HP, 2010)	0.36
"The aim of the study was to investigate the potential effect of short, moderate intensity (≤70% maximum heart rate) cyclette exercise on levodopa (LD)/dopa decarboxylase inhibitor bioavailability and motor response in a subgroup of Parkinson disease (PD) patients presenting a moderate-to-severe delay in fasting morning LD dose absorption and matched motor response."	( The effect of a clinically practical exercise on levodopa bioavailability and motor response in patients with Parkinson disease. Albani, F; Baruzzi, A; Contin, M; Lopane, G; Martinelli, P; Scaglione, C, )	0.59
" Levodopa/carbidopa/entacapone (LCE) provides higher bioavailability of levodopa compared with levodopa/carbidopa formulations and has been shown to be effective in PD patients with wearing-off symptoms."	( Night-time bioavailability of levodopa/carbidopa/entacapone is higher compared to controlled-release levodopa/carbidopa. Ellmén, J; Kailajärvi, M; Korpela, K; Kuoppamäki, M; Lehtinen, T; Sauramo, A; Vahteristo, M, 2010)	1.56
"A single evening dose of LCE 200 was associated with significantly better bioavailability compared with CR-LC 200."	( Night-time bioavailability of levodopa/carbidopa/entacapone is higher compared to controlled-release levodopa/carbidopa. Ellmén, J; Kailajärvi, M; Korpela, K; Kuoppamäki, M; Lehtinen, T; Sauramo, A; Vahteristo, M, 2010)	0.65
"The results of this study demonstrate that a single bedtime dose of LCE 200 provides higher bioavailability of levodopa compared to CR-LC 200."	( Night-time bioavailability of levodopa/carbidopa/entacapone is higher compared to controlled-release levodopa/carbidopa. Ellmén, J; Kailajärvi, M; Korpela, K; Kuoppamäki, M; Lehtinen, T; Sauramo, A; Vahteristo, M, 2010)	0.86
" With the aim of increasing the bioavailability of L: -dopa (LD) after oral administration and of overcoming the pro-oxidant effect associated with LD therapy, we designed a peptidomimetic LD prodrug (1) able to release the active agent by enzyme catalyzed hydrolysis."	( CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug. Cacciatore, I; Cerasa, LS; Cornacchia, C; Di Stefano, A; Fontana, A; Iannitelli, A; Mollica, A; Nasuti, C; Pinnen, F; Sozio, P, 2012)	0.38
"The controlled-release preparations of levodopa or newer soluble preparations of levodopa may improve levodopa bioavailability and tolerability and help managing (or even preventing) motor complications."	( Soluble and controlled-release preparations of levodopa: do we really need them? Berardelli, A; Bloise, M; Di Stasio, F; Fabbrini, G, 2010)	0.89
" MRZ-8676 (6,6-dimethyl-2-phenylethynyl-7,8-dihydro-6H-quinolin-5-one) is a novel proprietary, selective, orally bioavailable mGluR5 NAM."	( Pharmacological characterization of MRZ-8676, a novel negative allosteric modulator of subtype 5 metabotropic glutamate receptors (mGluR5): focus on L: -DOPA-induced dyskinesia. Danysz, W; Dekundy, A; Gravius, A; Hechenberger, M; Mela, F; Nagel, J; Parsons, CG; Pietraszek, M; Tober, C; van der Elst, M, 2011)	0.37
" It has been reported that the bioavailability of LD is higher in elderly patients than in young patients; however, it is not known how ageing changes the bioavailability of LD among elderly patients."	( Influence of ageing on the pharmacokinetics of levodopa in elderly patients with Parkinson's disease. Hamamoto, M; Katayama, Y; Kumagai, T; Nagayama, H; Nishimura, S; Nishiyama, Y; Tsukamoto, K; Ueda, M, 2011)	0.63
"Absorption of the levodopa/carbidopa gel can be adequately described with first-order absorption with bioavailability and lag time."	( A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion. Dougherty, M; Groth, T; Karlsson, MO; Nyholm, D; Pålhagen, S; Westin, J; Willows, T, )	0.71
" Levodopa bioavailability was higher on day 2 due to the COMT inhibition."	( Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson's disease. Muhlack, S; Müller, T; Woitalla, D, 2011)	1.5
"Levodopa moderately increased bioavailability of nerve growth factor and growth hormone combined with the rise of levodopa."	( Levodopa induces synthesis of nerve growth factor and growth hormone in patients with Parkinson disease. Hellwig, R; Muhlack, S; Müller, T, )	3.02
"The aim of this study was to evaluate the fasting bioavailability of a new generic formulation of levodopa 200 mg/benserazide 50 mg tablets (test) and compare this generic formulation with the branded formulation (reference) to meet regulatory criteria for marketing the test product in Argentina."	( Comparative bioavailability of 2 tablet formulations of levodopa/benserazide in healthy, fasting volunteers: a single-dose, randomized-sequence, open-label crossover study. Assefi, AR; Bertuola, R; Czerniuk, P; Di Girolamo, G; Keller, GA; Spatz, JG, 2011)	0.83
" The main factors responsible for the poor bioavailability are the drug's physical-chemical properties: low water and lipid solubility, resulting in unfavorable partition, and the high susceptibility to chemical and enzymatic degradation."	( L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment. Cerasa, LS; Di Stefano, A; Iannitelli, A; Sozio, P, 2011)	0.37
" Thus, to the extent that somatodendritic DA release affects behavior, TH regulation in the midbrain may be critical for DA bioavailability to influence behavior."	( Dichotomy of tyrosine hydroxylase and dopamine regulation between somatodendritic and terminal field areas of nigrostriatal and mesoaccumbens pathways. Pruett, BS; Salvatore, MF, 2012)	0.38
"To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers."	( Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Aquilonius, SM; Bäckström, T; Ehrnebo, M; Gomes-Trolin, C; Lewander, T; Nyholm, D; Nyström, C; Panagiotidis, G, )	0.68
" However, bioavailability of drugs varies between species and it is unknown how plasma L-DOPA levels providing therapeutic benefit in the non-human primate compare to those having similar actions in PD patients."	( L-DOPA pharmacokinetics in the MPTP-lesioned macaque model of Parkinson's disease. Brotchie, JM; Fox, SH; Huot, P; Johnston, TH; Koprich, JB, 2012)	0.38
"The results demonstrate that coadministration of domperidone increased the bioavailability of levodopa."	( Coadministration of domperidone increases plasma levodopa concentration in patients with Parkinson disease. Iwaki, H; Nagai, M; Nishikawa, N; Nomoto, M; Tsujii, T; Yabe, H, )	0.6
" The low bioavailability of L-Dopa may cause a wide variation in clinical response between patients."	( Protective effects of L-dopa and carbidopa combined treatments on human catecholaminergic cells. Colamartino, M; Cornetta, T; Cozzi, R; Leone, S; Meneghini, C; Padua, L; Testa, A, 2012)	0.38
" It is anticipated that the recent development of mGlu4 PAMs with improved systemic bioavailability will facilitate progression of these agents into the primate model of PD where their potential can be further explored."	( Targeting glutamate receptors to tackle the pathogenesis, clinical symptoms and levodopa-induced dyskinesia associated with Parkinson's disease. Duty, S, 2012)	0.61
" The stronger in vivo effect of (+)-catechin on L-DOPA methylation compared to the other dietary compounds is due to its better bioavailability in vivo."	( Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration. Fukui, M; Kang, KS; Wen, Y; Yamabe, N; Zhu, BT, 2013)	0.65
" In the present study, poly(butylene succinate) (PBSu) microspheres-based drug delivery system to improve the bioavailability of the drug levodopa was evaluated for the first time."	( Development of poly(butylene succinate) microspheres for delivery of levodopa in the treatment of Parkinson's disease. Krishnan, UM; Mohanraj, K; Sethuraman, S, 2013)	0.83
" Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery."	( Design of an interpolyelectrolyte gastroretentive matrix for the site-specific zero-order delivery of levodopa in Parkinson's disease. Choonara, YE; du Toit, LC; Kumar, P; Modi, G; Ndesendo, VM; Ngwuluka, NC; Pillay, V, 2013)	0.8
"Orally LD-treated patients with Parkinson disease had a lower LD dose compared with the ones on an LD infusion, but LD, 3-OMD, and homocysteine bioavailability was not different."	( Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease. Jugel, C; Klostermann, F; Muhlack, S; Müller, T, )	0.13
" It is characterized by improved bioavailability allowing dose reduction and a lower exposure to amphetamine metabolites."	( The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson's disease. Magyar, K; Szökő, E; Tábi, T; Vécsei, L, 2013)	0.39
"Levodopa is the drug of choice in the treatment of Parkinson's disease but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation."	( Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Lohan, S; Murthy, RS; Sharma, S, 2014)	2.06
" On the other hand, it has been recently reported that impaired arginine transport contributes to low renal nitric oxide bioavailability observed in the SHR renal medulla."	( Renal amino acid transport systems and essential hypertension. Pinho, MJ; Pinto, V; Soares-da-Silva, P, 2013)	0.39
"Entacapone increases the bioavailability of levodopa and simultaneously alleviates partially its resulting hyperhomocysteinemia."	( [Effects of entacapone on plasma homocysteine in Parkinson's disease patients on levodopa]. Li, Q; Liu, W; Sun, YN; Wang, Y; Yang, JF; Zhang, BS; Zhang, W; Zhao, P, 2013)	0.88
" The pharmacokinetic analyses demonstrated relatively low bioavailability for L-dopa and adequate plasma levels of pramipexole, even at baseline, on a stable daily dose."	( Therapeutic response to pramipexole in a patient with multiple system atrophy with predominant parkinsonism: positron emission tomography and pharmacokinetic assessments. Ishii, K; Katayama, Y; Nagayama, H; Nakajima, N; Nishiyama, Y; Ueda, M, 2013)	0.39
" Entacapone, a catechol-O-methyltransferase inhibitor, can also be used to improve the bioavailability of levodopa, especially when used in conjunction with a DDCI."	( Levodopa in the treatment of Parkinson's disease: current status and new developments. Salat, D; Tolosa, E, 2013)	2.05
"The present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-O-methyltransferase (COMT) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey."	( Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor. Bonifácio, MJ; Soares-da-Silva, P; Sutcliffe, JS; Torrão, L; Wright, LC, 2014)	0.85
" This effort led to the discovery of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine (PF470, 14) as a highly potent, selective, and orally bioavailable mGluR5 NAM."	( Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulat Balan, G; Barreiro, G; Boscoe, BP; Chen, L; Chenard, LK; Cianfrogna, J; Claffey, MM; Coffman, KJ; Drozda, SE; Dunetz, JR; Fonseca, KR; Galatsis, P; Grimwood, S; Lazzaro, JT; Mancuso, JY; Miller, EL; Reese, MR; Rogers, BN; Sakurada, I; Shaffer, CL; Skaddan, M; Smith, DL; Stepan, AF; Trapa, P; Tuttle, JB; Verhoest, PR; Walker, DP; Wright, AS; Zaleska, MM; Zasadny, K; Zhang, L, 2014)	0.4
" Available controlled release levodopa formulations produce more sustained plasma levels but also show lower bioavailability and slower time to peak, resulting in poor clinical outcome especially in advanced patients."	( Novel levodopa formulations in the treatment of Parkinson's disease. Antonini, A; Pilleri, M, 2014)	1.17
"LCIG administration results in faster absorption, comparable levodopa bioavailability and significantly reduced intra-subject variability in levodopa concentrations relative to LC-oral administration."	( Population pharmacokinetics of levodopa in subjects with advanced Parkinson's disease: levodopa-carbidopa intestinal gel infusion vs. oral tablets. Dutta, S; Othman, AA, 2014)	0.93
" Development of COMT inhibitors can efficiently increase the bioavailability of L-dopa."	( Inhibition of catechol-o-methyltransferase (COMT) by myricetin, dihydromyricetin, and myricitrin. Jia, YH; Zhu, X, 2014)	0.4
" Maximum concentration, time to maximum level and bioavailability of levodopa did not differ between all conditions each with 200 mg levodopa application as a whole."	( Fewer fluctuations, higher maximum concentration and better motor response of levodopa with catechol-O-methyltransferase inhibition. Herrmann, L; Muhlack, S; Müller, T; Salmen, S, 2014)	0.87
"Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition."	( Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations. Falcão, A; Lopes, N; Nunes, T; Pinto, R; Rocha, JF; Santos, A; Soares-da-Silva, P; Vaz-da-Silva, M; Wright, LC, 2014)	0.87
" Aim of this study was to test the efficacy of liquid levodopa with higher bioavailability in patients with SIBO."	( Liquid melevodopa versus standard levodopa in patients with Parkinson disease and small intestinal bacterial overgrowth. Bentivoglio, AR; Bove, F; Fasano, A; Fortuna, S; Gabrielli, M; Gasbarrini, A; Marconi, S; Ragazzoni, E; Tortora, A; Zocco, MA, )	0.8
"L-DOPA has long been the 'gold standard' treatment for Parkinson's disease (PD), but suffers from poor oral bioavailability and rapid pharmacokinetic elimination."	( IPX066 , a mixed immediate/sustained-release levodopa preparation for Parkinson's disease. Ondo, W, 2014)	0.66
" Limitations in its bioavailability and tolerability led to the search for drugs that could improve its pharmacokinetics and safety profile."	( Improving L-dopa therapy: the development of enzyme inhibitors. Gershanik, OS, 2015)	0.42
" Sex differences in the bioavailability of LD have been shown previously."	( Sex differences in the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Kumagai, T; Mishina, M; Nagayama, H; Nishiyama, Y; Ota, T; Ueda, M, )	0.39
"Even in the elderly cohort, the women had a significantly greater bioavailability of LD."	( Sex differences in the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Kumagai, T; Mishina, M; Nagayama, H; Nishiyama, Y; Ota, T; Ueda, M, )	0.39
"Opicapone has a prolonged inhibitory effect on peripheral COMT, which extends the bioavailability of levodopa, without inducing toxicity."	( Pharmacological profile of opicapone, a third-generation nitrocatechol catechol-O-methyl transferase inhibitor, in the rat. Bonifácio, MJ; Loureiro, AI; Palma, PN; Soares-da-Silva, P; Torrão, L; Wright, LC, 2015)	0.63
" In this work, the combined use of l-DOPA methylester hydrochloride prodrug (LDME) with transbuccal drug delivery was supposed as a good alternative method to optimize the bioavailability of l-DOPA, to maintain constant plasma levels and to decrease the drug unwanted effects."	( Potential transbuccal delivery of l-DOPA methylester prodrug: stability in the environment of the oral cavity and ability to cross the mucosal tissue. Campisi, G; De Caro, V; Giannola, LI; Scaturro, AL, 2016)	0.43
" Bioavailability of LD from ER CD-LD was 83."	( Comparison of the pharmacokinetics of an oral extended-release capsule formulation of carbidopa-levodopa (IPX066) with immediate-release carbidopa-levodopa (Sinemet(®)), sustained-release carbidopa-levodopa (Sinemet(®) CR), and carbidopa-levodopa-entacapo Gupta, S; Hsu, A; Modi, NB; Yao, HM, 2015)	0.64
" Levodopa bioavailability was 99 % for LCIG relative to LC-oral."	( Jejunal Infusion of levodopa-carbidopa intestinal gel versus oral administration of levodopa-carbidopa tablets in japanese subjects with advanced Parkinson's disease: pharmacokinetics and pilot efficacy and safety. Benesh, J; Chatamra, K; Dutta, S; Mohamed, ME; Nagai, M; Othman, AA; Yanagawa, M, 2015)	1.65
" Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa-levodopa, the median dosages correspond to ~500 and ~1015 mg/day of IR levodopa in early and advanced PD, respectively."	( Long-Term Treatment with Extended-Release Carbidopa-Levodopa (IPX066) in Early and Advanced Parkinson's Disease: A 9-Month Open-Label Extension Trial. Dzyak, L; Gupta, S; Hsu, A; Kell, S; Khanna, S; Nausieda, P; Rudzinska, M; Silver, DE; Spiegel, J; Tsurkalenko, ES; Waters, CH, 2015)	0.89
"Our results show an impaired LD bioavailability from Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase inhibitors coadministration, which might explain the suggested lower dyskinetic potential of Mucuna compared with standard LD formulations."	( Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations. Contin, M; Guarino, M; Iannello, C; Lopane, G; Passini, A; Poli, F, )	0.36
"Adequate treatment of Parkinson's patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action."	( A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods. de Boer, AH; Frijlink, HW; Grasmeijer, F; Hagedoorn, P; Luinstra, M; Moes, JR, 2015)	1.36
" These results indicate that soy partly increased the bioavailability of levodopa and suppressed levodopa degradation through COMT."	( Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens. Ito, H; Koh, J; Kondo, T; Nagashima, Y; Sakata, M, 2016)	0.92
"Parkinson's disease is a motor dysfunction that has been widely studied but many of the reports on commercial drugs for the treatment of this disease have afforded some undesirable side effects that generate an extensive and unviable treatment by economic costs and due to the bioavailability of the assayed compounds."	( Aporphines and Parkinson's Disease: Medical Tools for the Future. Fazel Nabavi, S; Modak, B; Rastrelli, L; Sobarzo-Sánchez, E; Uriarte, E, 2016)	0.43
" The water solubility and improved bioavailability may help reduce medication frequency associated with l-DOPA treatment of PD."	( DopAmide: Novel, Water-Soluble, Slow-Release l-dihydroxyphenylalanine (l-DOPA) Precursor Moderates l-DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons. Atlas, D, 2016)	0.43
" Efforts have been made recently to improve levodopa bioavailability either by developing more effective oral formulations or by innovating routes of administration (intestinal infusion, transcutaneous or inhaled levodopa)."	( Novel Levodopa Formulations for Parkinson's Disease. Fox, SH; Freitas, ME; Ruiz-Lopez, M, 2016)	1.18
"Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition."	( Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics. Almeida, L; Bonifácio, MJ; Falcão, A; Fauchoux, N; Loureiro, AI; Nunes, T; Pinto, R; Rocha, JF; Santos, A; Sicard, É; Soares-da-Silva, P, 2017)	0.95
"Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy."	( Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson's disease treated with L-DOPA. Ferreira, J; Lees, AJ; Poewe, W; Rascol, O; Reichmann, H; Stocchi, F; Tolosa, E, 2017)	0.46
"Levodopa bioavailability is enhanced by adding entacapone."	( Levodopa dose maintenance or reduction in patients with Parkinson's disease transitioning to levodopa/carbidopa/entacapone. Baik, JS; Cho, JW; Kim, Y; Koh, SB; Lee, JY; Lee, PH; Park, J; Sohn, YH; Youn, J, )	3.02
" The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of Levodopa drug."	( Nanocarrier for levodopa Parkinson therapeutic drug; comprehensive benserazide analysis. Etminan, N; Rahmanifar, E; Yoosefian, M, 2018)	1.03
" Peripheral catechol-O-methyltransferase (COMT) inhibition improves the bioavailability of levodopa and results in a prolonged response."	( Are There Benefits in Adding Catechol-O Methyltransferase Inhibitors in the Pharmacotherapy of Parkinson's Disease Patients? A Systematic Review. Katsaiti, I; Nixon, J, 2018)	0.7
" At the same time, measurements of LD and dopamine of mice administered with this formulation showed enhanced bioavailability of LD."	( Improved Bioavailability of Levodopa Using Floatable Spray-Coated Microcapsules for the Management of Parkinson's Disease. Baek, JS; Ho, HK; Lim, KL; Loo, SCJ; Pang, YY; Tan, EY; Tee, JK, 2018)	0.77
" Current research aims to increase drug bioavailability and to deliver it to the brain continuously."	( Long-term management of Parkinson's disease using levodopa combinations. Möhr, JD; Müller, T, 2018)	0.73
" The most widely used MAO-B inhibitor to maintain the bioavailability of dopamine in the brain of PD patients is L-deprenyl, despite of its potential side-effects."	( Garcinol, an effective monoamine oxidase-B inhibitor for the treatment of Parkinson's disease. Bhattacharya, P; Borah, A; Chakrabarty, J; Dutta, A; Mazumder, MK; Paul, R; Phukan, BC, 2018)	0.48
" Expert opinion: CVT-301 may offer several potential advantages including increased systemic bioavailability through pulmonary absorption, rapid onset of action, avoidance of first-pass drug metabolism and less plasma-level variability."	( Pharmacokinetic drug evaluation of CVT-301 for the treatment of Parkinson's disease. Stirpe, P; Stocchi, F; Torti, M; Vacca, L, 2018)	0.48
"Levodopa (LEVO) as the gold standard in the treatment of Parkinson's disease is usually administrated per os but its bioavailability is low."	( Interaction Studies Between Levodopa and Different Excipients to Develop Coground Binary Mixtures for Intranasal Application. Alapi, T; Ambrus, R; Bartos, C; Katona, G; Kiss, T; Szabó-Révész, P; Varga, G, 2019)	2.25
" The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa."	( Old Drugs, New Delivery Systems in Parkinson's Disease. Gupta, HV; Lyons, KE; Pahwa, R, 2019)	0.71
" Amantadine ER provides higher and more continuous amantadine plasma bioavailability than conventional immediate-release formulations, which require administration up to three times daily."	( Recent Clinical Advances in Pharmacotherapy for Levodopa-Induced Dyskinesia. Möhr, JD; Müller, T, 2019)	0.77
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
"Both the ODE and the SDE models estimated bioavailability to be approximately 75%."	( Investigating Stochastic Differential Equations Modelling for Levodopa Infusion in Patients with Parkinson's Disease. Alam, M; Rönnegård, L; Saqlain, M; Westin, J, 2020)	0.8
" Levodopa is the drug of choice in the treatment of PD but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation."	( Arisoy, S; Atalay, O; Comoglu, T; Onal, D; Pehlivanoglu, B; Sayiner, O, 2020)	1.47
" Opicapone is a recent and selective third-generation COMT inhibitor which achieves marked increase in the bioavailability of levodopa."	( Optimized clinical management of Parkinson's disease with opicapone. Recommendations from Spanish experts. García Ruiz-Espiga, P; Linazasoro-Cristóbal, G; López Del Val, LJ; López-Manzanares, L; Luquin-Piudo, MR; Martínez-Castrillo, JC; Mir, P; Pagonabarraga-Mora, J, 2020)	0.76
" The final model was a one compartment model with a high fixed absorption rate constant, and a first order elimination, with estimated apparent clearances (CL/F), of 27."	( Population pharmacokinetics of levodopa gel infusion in Parkinson's disease: effects of entacapone infusion and genetic polymorphism. Nielsen, EI; Nyholm, D; Senek, M, 2020)	0.84
" It is widely accepted that levodopa needs to be administered using formulations that result in good and consistent bioavailability and the physiologically relevant and continuous formation of dopamine in the brain to maximise its efficacy while avoiding and reversing 'wearing off' and dyskinesia."	( Improving the Delivery of Levodopa in Parkinson's Disease: A Review of Approved and Emerging Therapies. Chaudhuri, KR; Jenner, P; Qamar, MA; Urso, D, 2020)	1.15
" Eradication of the infection improves levodopa response in Parkinson's disease, likely as a consequence of an increased oral pre-systemic bioavailability of levodopa, likely to be explained by reduced Helicobacter-dependent levodopa consumption in the stomach."	( Effects of Helicobacter pylori on Levodopa Pharmacokinetics. Hellström, PM; Nyholm, D, 2021)	1.17
"Eradication of Helicobacter pylori improves levodopa bioavailability resulting in improved motor control."	( Effects of Helicobacter pylori on Levodopa Pharmacokinetics. Hellström, PM; Nyholm, D, 2021)	1.16
" Pharmacokinetic parameters including bioavailability of 75 and 85% with mean residence time of 78 and 94 min were estimated for intranasal solution and thermosensitive gel using the validated HPLC method, which indicated that levodopa nasal gel may be a good alternative with appropriate pharmacokinetic outcome."	( Rapid High-Performance Liquid Chromatography Method for Levodopa Quantitation at Low UV Wavelength: Application of Pharmacokinetics Study in Rat Following Intranasal Delivery. Alipour, S; Mohammadi, Z; Parhizkar, E, 2021)	1.05
"The presence of carbidopa increases the bioavailability of levodopa within the eye, enhancing its antimyopic effects, with topical application showing the greatest efficacy."	( Coadministration With Carbidopa Enhances the Antimyopic Effects of Levodopa in Chickens. Ashby, R; Karouta, C; Kelly, T; Morgan, I; Thomson, K, 2021)	1.1
"Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used hypoglycaemic agents and improve glucose metabolism by enhancing the bioavailability of active glucagon-like peptide-1."	( Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson's disease. Baik, K; Chung, SJ; Hong, N; Jeong, SH; Jung, JH; Lee, PH; Lee, YH; Sohn, YH; Yoo, HS, 2021)	0.62
" Here, a microstirring pill technology is reported with built-in mixing capability for oral drug delivery that greatly enhances bioavailability of its therapeutic payload."	( A Microstirring Pill Enhances Bioavailability of Orally Administered Drugs. Esteban-Fernández de Ávila, B; Fang, RH; Karshalev, E; Litvan, I; Mundaca-Uribe, R; Nguyen, B; Wang, J; Wei, X; Zhang, L, 2021)	0.62
" However, oral L-DOPA exhibits low oral bioavailability, limited brain uptake, peripheral DA-mediated side effects and its poor brain bioavailability can lead to long-term complications."	( Particulate levodopa nose-to-brain delivery targets dopamine to the brain with no plasma exposure. Akcan, O; Dimiou, S; Huang, H; Kubajewska, I; Lopes, RM; Mellor, RD; Schätzlein, AG; Schlosser, CS; Shet, MS; Uchegbu, IF; Whiteside, GT, 2022)	1.1
" Levodopa bioavailability and its maximum concentration were higher with opicapone."	( Effects of One-Day Application of Levodopa/Carbidopa/Entacapone versus Levodopa/Carbidopa/Opicapone in Parkinson's Disease Patients. Müller, T; Schlegel, E; Thiede, HM; Zingler, S, 2022)	1.91
"AsA can mitigate the degradation of carbidopa induced by MgO and may contribute to improving the bioavailability of levodopa in patients with PD."	( Ascorbic acid can alleviate the degradation of levodopa and carbidopa induced by magnesium oxide. Kubo, M; Miyaue, N; Nagai, M, 2022)	1.19
"Combining opicapone 50 mg with a 100 mg lower daily dose of levodopa provides higher levodopa bioavailability with avoidance of trough levels."	( Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease. Antonini, A; Ferreira, JJ; Guimarães, B; Moreira, J; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P; Stocchi, F, 2022)	1.27
" The metabolism of levodopa in the periphery not only decreases its bioavailability but also affects its efficacy."	( Relationship Between Gut Bacteria and Levodopa Metabolism. Sheng, S; Xu, K; Zhang, F, 2023)	1.51
" To show that generic drugs are equivalent to the originator drug, regulations usually refer to the bioavailability of active ingredients, which is influenced by the selected dosage form and the chosen excipients."	( Different dissolution conditions affect stability and dissolution profiles of bioequivalent levodopa-containing oral dosage forms. Langer, K; Rose, O; Weitzel, J; Wünsch, A, 2022)	0.94
" The implementation of drug delivery systems allows to bypass problems related to irregular and often unpredictable intestinal absorption of oral levodopa, which significantly affects its bioavailability and contributes to the development and persistence of motor complications."	( Current and novel infusion therapies for patients with Parkinson's disease. Antonini, A; D'Onofrio, V; Guerra, A, 2023)	1.11
" Analysis of experimental results using the model revealed that levodopa is well absorbed throughout the entire small intestine (i."	( Model-based optimization of controlled release formulation of levodopa for Parkinson's disease. Arav, Y; Zohar, A, 2023)	1.39

Dosage Studied

Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall. abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen. Tolerance to levodOPA should be considered in establishing oral dosing regimens.

Excerpt	Relevance	Reference
" In 5 previously untreated patients, (-)-deprenyl alone gave no benefit, but when it was used with levodopa and carbidopa a mean dosage reduction of 200 mg levodopa daily was possible."	( Deprenyl in Parkinson's disease. Elsworth, JD; Kohout, LJ; Lees, AJ; Sandler, M; Shaw, KM; Stern, GM; Youdim, MB, 1977)	0.47
" The main problems were psychiatric disturbance (8 patients) and erythromelalgia (7 patients); these effects tended to occur late (mean 6 months and 10 months, respectively) and with high dosage (mean 66 mg and 115 mg daily)."	( Long-term treatment of parkinsonism with bromocriptine. Calne, DB; Neophytides, A; Nutt, JG; Plotkin, C; Teychenne, PF; Williams, AC, 1978)	0.26
"Gamma hydroxybutyrate (GHB) was administered intravenously to monkeys that had been pretreated orally for 2 weeks with various anticonvulsant drugs or with L-DOPA at different dosage levels."	( Gamma hydroxybutyrate in the monkey. II. Effect of chronic oral anticonvulsant drugs. Snead, OC, 1978)	0.26
" Dosage is the only other factor differentiating the two groups of Parkinsonians treated."	( Plasmatic renin activity in patients treated with L-dopa and inhibitor of dopa decarboxylase (IDC). Allain, H; Bentue-Ferrer, D; Madigand, M; Pape, D; Reymann, JM; Van den Driessche, J, 1979)	0.26
" FS-32 showed anti-reserpine activity in a dose-dependent manner, whereas imipramine exhibited a bell-shaped dose-response pattern."	( Pharmacological studies on a new thymoleptic antidepressant, 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32). Fujimura, Y; Ikeda, Y; Iwasaki, T; Koide, T; Matsushita, H; Nagashima, R; Shindo, M; Shiraki, Y; Suzuki, S; Takano, N, 1979)	0.26
" The increase was blocked by phenoxybenzamine at a dosage level of 20 mg/kg which did not, of itself, reduce flexor reflex amplitude."	( A system for measuring the noradrenaline receptor contribution to the flexor reflex. Austin, JH; Fuxe, K; Nygren, LG, 1976)	0.26
" With l-dopa it was antogonised when the dose of morphine was minimal but with increased dosage of morphine, there was no significant effect."	( Morphine analgesia and its modification by drugs altering serotonin (5-HT) and dopamine levels in the brain. Gupta, SK; Shinde, S, )	0.13
"Radioimmunological methods have been used to assay the plasma concentrations of gonadotropins, androgens (expressed as the sum of testosterone and dihydrotestosterone) and 17beta-oestradiol in 98 patients suffering from dysspermia of variable etiology, after stimulation with GnRH, Clomiphene, L-Dopa, Cyclophenyl, HCG in various dosage schemes, and HMG."	( [Dynamic tests with GnRH, L-dopa, clomiphene, cyclophenyl, HCG and HMG in 98 cases of dysspermia due to a variety of causes]. De Aloysio, D; Farello, P; Flamigni, C; Fronticelli, A; Nardi, M; Venturoli, S, 1977)	0.26
" The dosage of nomifensine started at 50 mg, was increased to 150 mg daily, and other medication was continued unchanged."	( Nomifensine in Parkinson's disease. Bedard, P; Marsden, CD; Parkes, JD, 1977)	0.26
" By the use of the combination preparation, the daily dosage of levodopa could be reduced by 77%."	( A comparative clinical investigation of the therapeutic effect of levodopa alone and in combination with a decarboxylase inhibitor (carbidopa) in cases of Parkinson's disease. Dorner, A; Wajsbort, E; Wajsbort, J, 1978)	0.73
" Mean daily maintenance dosage was 612."	( Levodopa/benserazide ('Madopar') combination therapy in elderly patients with parkinsonism. Carlyle, D; Williams, BO, 1979)	1.7
" Reduction of levodopa dosage to one sixth with the aid of a peripheral decarboxylase inhibitor (benserazide) largely eliminated autoimmune haemolysis while maintaining adequate control of neurologic symptoms."	( Dose-related levodopa-induced haemolytic anaemia. Enström, MS; Liedén, G; Linström, FD, 1977)	0.99
" Frequent adjustment of levodopa dosage was necessary in view of continuing "on-off" fluctuations."	( Parkinsonism with 'on-off' phenomena. Intravenous treatment with levodopa after major abdominal surgery. Calne, DB; Devereux, D; Eng, N; Rosin, AJ, 1979)	0.8
" This abnormal involuntary posture was unaffected by manipulations of daily levodopa dosage and schedule, completely disappeared after withdrawal of drug therapy, and recurred following its readministration."	( Early-morning dystonia. A late side effect of long-term levodopa therapy in Parkinson's disease. Melamed, E, 1979)	0.74
" With both drugs, Madopar or Sinemet, an optimum therapeutic result was obtained with relatively small doses of L-dopa (the reduction in L-dopa dosage amounting to about 80%)."	( [The combined treatment of Parkinson's disease with L-dopa plus decarboxylase inhibitors (carbidopa, benserazide) (author's transl)]. Birkmayer, W; Mentasti, M; Podiwinsky, F; Riederer, P, 1979)	0.26
" Of 10 females dosed during pregnancy, 6 failed to deliver and lost substantially in body weight."	( Short- and long-term effects of a massive dose of 6-OH-DA upon marsh mice. Bischoff, F; Bryson, G, 1977)	0.26
" The treatment periods were 12 weeks; similar dosage schedules were used, with doses that induced equal levels of plasma levodopa in both combinations."	( Levodopa with benserazide or carbidopa in Parkinson disease. Mölsä, P; Rinne, UK, 1979)	1.91
" At both low (50 mg daily) and high (150 mg daily) dosage there was a similar but not identical profile of response."	( Comparison between lergotrile and bromocriptine in parkinsonism. Bern, SM; Calne, DB; McInturff, D; Pfeiffer, RF; Teychenne, PF, 1978)	0.26
" Paired ion chromatography also was tried successfully for the quantitative determinations of isoproterenol, levodopa, methyldopa, and phenylephrine in some dosage forms."	( Applications of paired ion high-pressure liquid chromatography to catecholamines and phenylephrine. Das Gupta, D; Ghanekar, AG, 1978)	0.47
" Chlorpromazine showed only a modest advantage over L-dopa and only on some Brief Psychiatric Rating Scale factor scores, and at maximum dosage the thought disturbance factor score in the L-dopa-treated group was not worse than at baseline."	( Paradoxical reaction to L-dopa in schizophrenic patients. Alpert, M; Diamond, F; Friedhoff, AJ; Marcos, LR, 1978)	0.26
" When a similar dosage regimen was employed with pregnant rats beginning on day 16 of gestation, levodopa plus carbidopa delayed the average delivery time 12 hr."	( Investigation of a dopaminergic mechanism for regulating oxytocin release. Lewis, PR; Miller, JW; Seybold, VS, 1978)	0.48
" The dosage was then increased until a consistent response was observed."	( The L-dopa on-off effect in Parkinson disease: treatment by transient drug withdrawal and dopamine receptor resensitization. Direnfeld, L; Marotta, J; Seeman, P; Spero, L, 1978)	0.26
" The combined administration of monoamine oxidase inhibitors with indirectly acting sympathomimetic amines will increase arterial pressure, but must be considered quite risky in light of inherently poor ability to regulate dose-response relationships and prior clinical experience with excessive arterial pressure elevation."	( Effect of selected drugs on arterial pressure response to upright posture. McNay, JL, 1976)	0.26
" Even so, plasma levodopa concentration correlates significantly with dosage size in a large parkinsonian population and also coincides with therapeutic response in many, but not all, patients."	( Clinical pharmacokinetics of levodopa in parkinson's disease. Bianchine, JR; Shaw, GM, 1976)	0.89
", circling behavior) in a spherical "rotometer" and dose-response relationships were generated using d-amphetamine, apomorphine, L-Dopa, haloperidol, and scopolamine."	( Drug-induced rotation in rats without lesions: behavioral and neurochemical indices of a normal asymmetry in nigro-striatal function. Glick, SD; Jerussi, TP, 1976)	0.26
" En 1974 nous avons proposé une méthode de dosage radio-immunologique homologue (A."	( [Dosage of prolactin in normal and pathological subjects (author's transl)]. Colin, C; Dourcy, C; Franchimont, P; Gaspard, U; Legros, JJ; Remacle, P; Reuter, A; van Cauwenberge, JR; Vrindts-Gevaert, Y, )	0.13
" The study was designed as paired series of growth hormone stimulation tests in which the effect of L-dopa alone, in different dosage schedules, was compared with the same dose level of L-dopa plus carbidopa, When L-dopa was given in full dose (125-500 mg), there was no significant difference in the serum GH concentrations at any time of sampling."	( The effect of L-dopa with and without decarboxylase inhibitor on growth hormone secretion in children with short stature. Aarskog, D; Fevang, FO; Stoa, RF; Thorsen, T, 1977)	0.26
" Level of dosage was hypothesized to have no differential effect on memory functioning."	( Levodopa, parkinsonism, and recent memory. Halgin, R; Misiak, H; Riklan, M, 1977)	1.7
" Generally the dosage range was up to a maximum of one tablet three times daily."	( [Treatment of Parkinson's disease with the combination drug L-carbidopa/L-dopa. Report on a 2 years study]. Hayek, J, 1977)	0.26
"A biphasic dose-response pattern is generated by the isoquinoline, 3-carboxysalsolinol, in analgesia tests conducted in mice."	( Analgesic effects of 3-carboxysalsolinol alone and in combination with morphine. Blum, K; Hirst, M; Marshall, A, 1977)	0.26
" The dose-response curves for the two last-mentioned dopamine metabolites closely follow those for MAO A and dopamine-deaminating activity, whether clorgyline or deprenil was used as MAO inhibitor."	( Preferential deamination of dopamine by an A type monoamine oxidase in rat brain. Delini-Stula, A; Maître, L; Waldmeier, PC, 1976)	0.26
" Within the dosage range studied, non-linear pharmacokinetics were observed for unchanged laevodopa, non-amino phenolic acids and dopamine but not for 3-O-methyldopa."	( Dose-dependent pharmacokinetics of laevodopa and its metabolites in the rat. Cheng, LK; Fung, HL, 1976)	0.26
" Side effects (hallucinations, confusion, dyskinesias) were frequent, but were usually reversible by lowering the dosage of levodopa or the accompanying anticholinergic medication."	( Piribedil: its synergistic effect in multidrug regimens for parkinsonism. Feigenson, JS; McDowell, FH; Sweet, RD, 1976)	0.46
" A reduced mean L-Dopa dosage was ruled out as the cause of this deterioration."	( Study of deterioration in long-term treatment of parkinsonism with L-dopa plus decarboxylase inhibitor. Bass-Verrey, F; Ludin, HP, 1976)	0.26
" The excitability of the superior cervical ganglion of the rat was not diminished after a three-day treatment with L-Dopa, Benseraside (Ro 4-4602/1) and Iproniazid, at a dosage below the toxic level (table I)."	( [Endogenous catecholamines and excitability of the superior cervical ganglion of the rat (author's transl)]. Burlet, DB, 1976)	0.26
" Although directly related to daily dosage of levodopa, the myoclonus was specifically blocked by the serotonin antagonist, methysergide."	( Levodopa-induced myoclonus. Bergen, D; Goetz, C; Klawans, HL, 1975)	1.96
" Dextroamphetamine in lower dosage also reduced disability by some 17 percent."	( Amphetamines in the treatment of Parkinson's disease. Asselman, P; Bovill, KT; Marsden, CD; Parkes, JD; Phipps, JA; Rose, P; Tarsy, D, 1975)	0.25
" Combination therapy resulted in a reduction in L-dopa dosage to 1/3 of the amount required during the baseline."	( Alpha methyldopahydrazine as an adjunct to levodopa therapy in Parkinson's disease. Jaatoul, N; Kertesz, A; McInnis, W; Paty, DW, 1975)	0.52
" Severe orthostatic light-headedness and frequent syncope had previously been alleviated only be reducing the dosage of levodopa to levels producing less than optimal antiparkinsonian benefits."	( Levodopa-induced postural hypotension. Treatment with fludrocortisone. Hoehn, MM, 1975)	1.91
" Second, dose-response relationships were established for the amphetamine enantiomers."	( Differences between (+)- and (-)-amphetamine in effects on locomotor activity and L-dopa potentiating action in mice. Strömberg, U; Svensson, TH, 1975)	0.25
" Clinical pharmacological studies disclosed that a 1 : 10 ratio of MK-486 to L-dopa in dosage was preferable."	( L-dopa therapy combined with peripheral decarboxylase inhibitor (MK-486) in Parkinsonism. Kishikawa, H; Ohmoto, T, 1975)	0.25
" Dose-response curves for apomorphine- and L-dopa-induced circling rates shifted to the left as the duration between the time of the 6-hydroxydopamine injection and the time of testing increased from 2 to 30 days."	( Supersensitivity to dopamine agonists following unilateral, 6-hydroxydopamine-induced striatal lesions in mice. Moore, KE; Thornburg, JE, 1975)	0.25
" Prolonged pretreatment with suprathreshold doses of amphetamine decreased the threshold dosage of both amphetamine and apomorphine necessary to elicit stereotyped behavior."	( Effect of chronic amphetamine exposure on stereotyped behavior: implications for pathogenesis of l-dopa-induced dyskinesias. Crossett, P; Dana, N; Klawans, HL, 1975)	0.25
" Time- and dose-response data with all three drugs suggest a direct inhibitory action on the caudate nucleus consistent with their proposed mechanism for treatment of Parkinson symptomatology."	( Head-turning induced by electrical stimulation of the caudate nucleus and its antagonism by anti-parkinson drugs. Barnett, A; Goldstein, J, 1975)	0.25
" These are predominantly involuntary movements and confusion, which can be eliminated by lowering the dosage of Deprenil."	( The potentiation of the anti akinetic effect after L-dopa treatment by an inhibitor of MAO-B, Deprenil. Birkmayer, W; Linauer, W; Riederer, P; Youdim, MB, 1975)	0.25
", were much higher in chronically dosed animals."	( Effects of chronic oral administration on the disposition of laevodopa and its major metabolites in the plasma of the rat. Cheng, LK; Fung, HL, 1975)	0.25
" At dosage with short intervals, the delay may cause an additive effect of two doses."	( Intestinal decarboxylation of orally administered L-dopa. Influence of pharmacological preparations, dose magnitude, dose sequence and food intake. Andersson, I; Granerus, AK; Jagenburg, R; Svanborg, A, 1975)	0.25
" Intraventricular injection of phenylephrine produced a dose-dependent hypothermia, whereas no dose-response relationship was obtained by isoproterenol."	( [Role of brain biogenic amines in the central thermoregulatory mechanism of the rat (author's transl)]. Fukushima, N, 1975)	0.25
" Observations were repeated with varying dosage patterns, showing variations but no substantial changes or disappearance of the symptoms described."	( [Long-term syndrome in the treatment of parkinsonism with L-dopa]. Chouza, C; Gomensoro, JB; Romero, S, 1975)	0.25
" Patients were allocated at random to treatment with either levodopa + benserazide ratio 4:1 (Madopar) or levodopa + carbidopa ratio 10:1 (Sinemet) using dosage schedules recommended by the manufacturers which they had to adhere to for 6 months."	( Parkinson's disease treated with Sinemet or Madopar. A controlled multicenter trial. Birket-Smith, E; Dupont, E; Hansen, E; Mikkelsen, B; Pakkenberg, H; Presthus, J; Rautakorpi, I; Riman, E; Rinne, UK, 1976)	0.5
" There was no difference between any of the groups as far as dosage of L-Dopa and clinical features."	( L-dopa in hepatic coma. Falcao, HA; Fischer, JE; Funovics, FJ; Wesdorp, RI, 1976)	0.26
"Observation of a 34-year-old woman receiving levodopa for familial torsion dystonia over a four-year period revealed that severe side effects (gastrointestinal problems, dyskinesias, cramps, anxiety) occurred with maximal dosage schedules during the first ten months of treatment."	( Long-term levodopa therapy for torsion dystonia. Herberg, KP; Still, CN, 1976)	0.92
" Animals were administered levodopa (levodopa with one-tenth dosage of carbidopa), carbachol or thrihexyphenidyl alone or administered in combination as levodopa (100 mg/kg) + carbachol, or levodopa+trihexyphenidyl given as a single bolus."	( Muscarinic cholinergic receptor-mediated modulation on striatal c-fos mRNA expression induced by levodopa in rat brain. Asanuma, M; Chou, H; Hirata, H; Mori, A; Ogawa, N, 1992)	0.8
" Abnormal movements accompany an overdose but regress when the dosage is decreased."	( [Dopa-sensitive dystonia]. Aicardi, J; Goutières, F; Rondot, P; Ziegler, M, 1992)	0.28
" Actual total daily levodopa dosage in patients treated with Sinemet CR was increased by 33%; however, the plasma level of this dosage is calculated to be similar to that of the previous dosage of Sinemet-STD (bio-availability of Sinemet CR is 71%)."	( Clinical efficacy of Sinemet CR 50/200 versus Sinemet 25/100 in patients with fluctuating Parkinson's disease. An open, and a double-blind, double-dummy, multicenter treatment evaluation. The Dutch Sinemet CR Study Group. Horstink, MW; Jansen, EN; Roos, RA; Wolters, EC, 1992)	0.61
" Verapamil, given for 1 week at a dosage of 240 mg orally to eight healthy volunteers, induced a significant elevation of basal PRL levels (17."	( Effects of calcium channel blockade with verapamil on the prolactin responses to TRH, L-dopa, and bromocriptine. Kamal, TJ; Molitch, ME, 1992)	0.28
"Irreversible inactivation of striatal D2 dopamine (DA) autoreceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or inactivation of striatal guanine nucleotide binding proteins (G proteins) with pertussis toxin (PT) shifted the dose-response curve for N-n-propylnorapomorphine (NPA)-mediated inhibition of gamma-butyrolactone (GBL)-induced elevation of L-3,4-dihydroxyphenylalanine (L-DOPA) to the right, with a decrease in the maximum response."	( The effects of pertussis toxin on dopamine D2 and serotonin 5-HT1A autoreceptor-mediated inhibition of neurotransmitter synthesis: relationship to receptor reserve. Bohmaker, K; Bordi, F; Meller, E, 1992)	0.28
" The results of the substitution phase show that combined treatment permitted a mean reduction of the levodopa dosage by 40%, without deterioration of therapeutic response."	( Primary combination therapy of early Parkinson's disease. A long-term comparison between the combined regimen bromocriptine/levodopa and levodopa monotherapy--first interim report. Kraus, PH; Letzel, H; Przuntek, H; Schwarzmann, D; Welzel, D, 1992)	0.71
" The women continue on a low dosage of levodopa after 9 and 13 years of treatment, with a stable, nearly complete, symptomatic response."	( Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia. Calne, DB; Fahn, S; Heiman, GA; Nygaard, TG; Snow, BJ; Takahashi, H, 1992)	0.55
" Also this result differs from what most authors have observed: they maintain that Horton's arteritis has become rather resistant to the cortisone therapy and required high dosage for a very long time."	( [Horton's bitemporal arteritis. A case report]. Carmenini, G; Di Maio, F; Martusciello, S; Meloni, F; Nicoletti, M; Scioli, A, 1992)	0.28
" dosage schedule."	( Comparative multiple-dose pharmacokinetics of controlled-release levodopa products. Collin, C; Eckernäs, SA; Grahnén, A; Ling-Andersson, A; Nilsson, M; Tiger, G, 1992)	0.52
" Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist."	( Optimization of levodopa therapy. Pfeiffer, R, 1992)	0.63
" Bioavailability of Sinemet CR levodopa is less than that of standard Sinemet, so a slightly higher total daily levodopa dose is required to achieve a comparable effect; but because Sinemet CR is absorbed much more slowly than is the standard preparation, dosing frequency can be reduced by up to half."	( The use of Sinemet CR in the management of mild to moderate Parkinson's disease. Rodnitzky, RL, 1992)	0.57
" Regular dosing with levodopa or apomorphine reliably resulted in peak dose dyskinesia."	( The use of thalamotomy in the treatment of levodopa-induced dyskinesia. Page, RD, 1992)	0.87
"Previous reports have shown that tolerance or sensitization to apomorphine depends on the dosage interval."	( Apomorphine lowers dopamine synthesis for up to 48 h: implications for drug sensitization. Castro, R; Rodriguez, M, 1991)	0.28
" Thirteen such patients, of mean age 78 y, without overt fluctuations in motor control in temporal relation to dosing with a levodopa/decarboxylase inhibitor combination, were studied."	( Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease. Bowes, SG; Deshmukh, AA; Dobbs, RJ; Dobbs, SM; Leeman, AL; Nicholson, PW; O'Neill, CJ, 1991)	0.8
" The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule."	( Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease. Albani, F; Baruzzi, A; Contin, M; Martinelli, P; Riva, R, 1991)	0.8
" We have studied the effects of multiple dosing of levodopa on gastric emptying and levodopa absorption in eight healthy young volunteers in a randomised two-way cross-over study."	( Gastric emptying in healthy volunteers after multiple doses of levodopa. George, CF; Macklin, B; Renwick, AG; Roseveare, C; Waller, DG, 1991)	0.77
" It is suggested that chlormethiazole is safe to use as a hypnotic at this dosage in this group of patients with Parkinson's disease, while temazepam did not appear to be effective as a hypnotic at this dosage."	( A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients. Ashwood, TJ; Bateman, DN; Tulloch, JA; Woodhouse, KW, 1991)	0.28
" The average daily levodopa dosing frequency did not change significantly during long-term treatment."	( Long-term evaluation of Sinemet CR in parkinsonian patients with motor fluctuations. Hutton, JT; Morris, JL, 1991)	0.61
" After 12 months, the mean dosage of levodopa was higher in the placebo group than in the lisuride group (318 +/- 121 and 274 +/- 74 mg daily respectively)."	( [Randomized study during a year of early combination of L-dopa/lisuride in Parkinson disease]. Fondarai, J; Petit, H; Vermersch, P, )	0.4
"Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time."	( Sinemet (CR4): an open-label study in moderately severe Parkinson's disease. Fritz, VU; Ming, A; Temlett, JA, 1991)	0.52
" Seven patients benefited after their dosing schedules were rearranged as a result of information gained from monitoring."	( Benefits of monitoring plasma levodopa in Parkinson's disease patients with drug-induced chorea. Mark, MH; McHale, DM; Sage, JI; Sonsalla, PK; Vitagliano, D, 1991)	0.57
" The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs."	( Characterisation of the in vivo behaviour of a controlled-release formulation of levodopa (Sinemet CR). Davis, SS; Evans, DF; Hardy, JG; Melia, CD; Short, AH; Sparrow, RA; Wilding, IR; Yeh, KC, 1991)	0.51
" Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'."	( Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety. Bulling, MT; Burns, RJ; Wing, LM, 1991)	0.61
" dosing (65 min), and bioavailability was 40%."	( Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary excretion of gamma-L-glutamyl-L-dopa in the rat. Cummings, J; Matheson, LM; Maurice, L; Smyth, JF, 1990)	0.28
" Using a MPTP dosing regimen a reversible parkinsonian-like syndrome was produced in the marmoset."	( Effects of classical and novel agents in a MPTP-induced reversible model of Parkinson's disease. Close, SP; Elliott, PJ; Hayes, AG; Marriott, AS, 1990)	0.28
" The dosage of agonist was gradually increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that of Sinemet was reduced concurrently."	( Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation. Cedarbaum, JM; Clark, M; Green-Parsons, A; Toy, LH, 1990)	0.28
" However significantly less frequent dosing was necessary with Sinemet CR."	( Sinemet CR in Parkinson's disease. Glaeske, CS; Hofman, R; Pfeiffer, RF; Wilken, KE, 1991)	0.28
" We carried out an oral levodopa dose-response study in two rhesus monkeys whose left hemiparkinsonism was induced by intracarotid administration of MPTP."	( Oral levodopa dose-response study in MPTP-induced hemiparkinsonian monkeys: assessment with a new rating scale for monkey parkinsonism. Gash, DM; Kim, MH; Kurlan, R, 1991)	1.1
" The methods have been utilized to evaluate the pharmacokinetics and bioavailability of oral dosage forms containing levodopa and carbidopa."	( Simultaneous high-performance liquid chromatographic analysis of carbidopa, levodopa and 3-O-methyldopa in plasma and carbidopa, levodopa and dopamine in urine using electrochemical detection. August, TF; Bayne, WF; Eisenhandler, R; Musson, DG; Titus, DC; Yeh, KC, 1990)	0.72
" When levodopa alone, or levodopa plus benserazide, was given as an acute challenge to animals receiving the same treatment chronically, it was found that levodopa alone still produced increases in striatal dopamine, DOPAC and HVA in those animals dosed chronically on levodopa, but it was less effective in this respect when given with benserazide to the animals dosed with levodopa plus benserazide."	( The effect of benserazide on the peripheral and central distribution and metabolism of levodopa after acute and chronic administration in the rat. Kent, AP; Stern, GM; Webster, RA, 1990)	0.98
" The negative aspects of Madopar HBS are a lower bioavailability that means a dosage increase and a longer latency for the therapeutic response in the morning."	( Long-term treatment with Madopar HBS in parkinsonians with fluctuations. Aljanati, R; Buzó, R; Caamaño, JL; Chouza, C; De Medina, O; Fernandez, A; Plachín, V; Romero, S; Scaramelli, A, 1990)	0.28
" The equivalent L-dopa dosage had to be increased by 56% (29-100%) with Madopar HBS while mean dopamine levels increased in four patients (by 47-257%) without the occurrence of peripheral side-effects."	( Controlled-release levodopa/benserazide (Madopar HBS): clinical observations and levodopa and dopamine plasma concentrations in fluctuating parkinsonian patients. Ceballos-Baumann, AO; Eckert, W; von Kummer, R; Weicker, H, 1990)	0.61
" The mean BP was reduced between 60 and 180 min after dosing in the patients, whereas such a reduction was not observed in 5 patients from whom L-dopa was withheld and in controls who showed a high ratio of plasma dopamine compared to plasma L-dopa after dosing."	( Hypotensive effect of long-term levodopa in patients with Parkinson's disease. Hamaguchi, K; Iwasaki, A; Iwasaki, S; Narabayashi, Y; Takakusagi, M, 1990)	0.56
" In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS."	( Madopar HBS in nocturnal symptoms of Parkinson's disease. Jansen, EN; Meerwaldtt, JD, 1990)	0.28
" Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily."	( Adjunctive therapy with bromocriptine in Parkinson's disease. Becker, AL; Bilchik, TR; Blumenfeld, A; Fourie, PB; Fritz, VU; Ming, A; Reef, HE; Saling, M; Temlett, JA, 1990)	0.28
" The degree of increase in the norepinephrine (NE) concentrations was closely correlated to the dosage of L-threo-DOPS."	( Effect of a synthetic norepinephrine precursor, L-threo-3,4- dihydroxyphenylserine on the total norepinephrine concentration in the cerebrospinal fluid of parkinsonian patients. Abe, T; Nozaki, Y; Takahashi, J; Takahashi, S; Tohgi, H; Ueno, M, 1990)	0.28
" However, the dose-response curves showed a marked (three- to fourfold) shift to the left in lesioned animals, indicating behavioural supersensitivity."	( Nigrostriatal damage is required for induction of dyskinesias by L-DOPA in squirrel monkeys. Boyce, S; Iversen, SD; Rupniak, NM; Steventon, MJ, 1990)	0.28
" Clinical improvement was associated with changes in several pharmacological indices: Acute dose-response studies of intravenous levodopa showed a shift of the curve to the right in the immediate postinfusion phase compared to preinfusion studies; the therapeutic index improved significantly as patients demonstrated about 76% increased beneficial antiparkinsonian response with an equal degree of toxic dyskinetic effects; and the duration of action of levodopa was prolonged by 30%."	( Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease. Baronti, F; Chase, TN; Heuser, IJ; Mouradian, MM, 1990)	0.72
"The acute dose-response profile of a standard oral levodopa dose was followed, over a maximum 8-h period, in 13 patients with and 10 patients without motor fluctuations using a battery of motor quantitative tests (tapping and walking speed, and multiple choice reaction and movement times)."	( Response to a standard oral levodopa test in parkinsonian patients with and without motor fluctuations. Avoni, P; Baruzzi, A; Contin, M; Cortelli, P; Martinelli, P; Procaccianti, G; Riva, R, 1990)	0.82
" Simultaneous clinical observation and determinations of plasma LD concentrations were often necessary to find the most efficacious dosing schedule for these patients."	( Complex dystonia of Parkinson's disease: clinical features and relation to plasma levodopa profile. McHale, DM; Sage, JI; Sonsalla, PK; Vitagliano, D, 1990)	0.5
" Linear calibration curves have been constructed by integrating the protonated molecular ion to silver ion peak area ratios over a known ion dosage and plotting versus the original sample concentration."	( Quantitative static secondary ion mass spectrometry of molecular ions from 1-beta-3,4-dihydroxyphenylalanine (L-dopa) and indolic derivatives. Clark, MB; Gardella, JA, 1990)	0.28
" These included the age at onset, the presenting symptom, the duration of illness, and the stage of the disease at the time of initiation of levodopa treatment as time-independent covariates, and the mean and last dosage of levodopa as time-dependent covariates."	( Response fluctuations in Parkinson's disease. Roos, RA; van der Velde, EA; Vredevoogd, CB, 1990)	0.48
" Dose-response curves for chorea and dystonia revealed that the same dose of L-dopa (30 mg/kg) induced the highest score for both dyskinesias: however, the severity was much greater for chorea."	( Characterisation of dyskinesias induced by L-dopa in MPTP-treated squirrel monkeys. Boyce, S; Iversen, SD; Rupniak, NM; Steventon, MJ, 1990)	0.28
" L-DOPA administration, consisting of a daily dosage of 600 mg plus 150 mg aromatic L-amino acid decarboxylase inhibitor was continued in all cases for at least 3 months."	( Unresponsiveness to L-DOPA in parkinsonian patients: a study of homovanillic acid concentration in the cerebrospinal fluid. Araki, H; Kondo, T; Muramoto, S; Narabayashi, H; Nishi, K; Takubo, H, 1989)	0.28
" The results suggest, the BH4 in the dosage used, is not effective in the treatment of Parkinson's disease."	( Tetrahydrobiopterin and Parkinson's disease. Dissing, IC; Gerdes, AM; Güttler, F; Lou, H; Lykkelund, C; Pakkenberg, H; Rasmussen, V, 1989)	0.28
" Thereafter, selegiline was added in a progressively increasing dosage up to a maximum of 10 mg/day during 4 months, with the aim of a) further improving the long-term results and b) reducing the doses of the new formula of L-DOPA."	( Combination of selegiline and controlled release levodopa in the treatment of fluctuations of clinical disability in parkinsonian patients. Aljanati, R; Buzo, R; Caamaño, JL; Chouza, C; De Medina, O; Fernandez, A; Romero, S; Scaramelli, A, 1989)	0.53
" Selegiline treatment allowed a significant reduction of the necessary daily levodopa dose in both parts of the study and of the daily dosing frequency in the long-term investigation."	( Selegiline and levodopa in early or moderately advanced Parkinson's disease: a double-blind controlled short- and long-term study. Boesen, F; Dupont, E; Heinonen, E; Mikkelsen, B; Mogensen, P; Rasmussen, C; Sivertsen, B, 1989)	0.86
" Its administration with levodopa, as initial therapy, allows for use of lower dosage and less side-effects of the latter agent."	( Selegiline in the treatment of Parkinson's disease--long term experience. Elizan, TS; Moros, D; Yahr, MD, 1989)	0.58
" A daily levodopa dosage of at least 4 g appears to a prerequisite for long-term response to the drug."	( Clinical relevance of long-term therapy with levodopa and orally active dopamine analogues in patients with chronic congestive heart failure. Hasenfuss, G; Just, H, 1989)	0.95
" We performed a dosage ranging and placebo crossover study in six patients to evaluate the efficacy and tolerance of CV when used as an adjunct to Sinemet in patients with Parkinson's disease."	( CV 205-502: safety, tolerance to, and efficacy of increasing doses in patients with Parkinson's disease in a double-blind, placebo crossover study. Gauger, LL; Olanow, CW; Werner, EG, 1989)	0.28
" Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry."	( Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa. Gilley, DW; Goetz, CG; Klawans, HL; Tanner, CM, 1989)	0.7
" The daily dosage after 1 year, 766 mg +/- 250 mg, was increased by 23% compared with standard Sinemet dosage, without additional secondary effects."	( Effect of controlled-release carbidopa/levodopa on motor performance in advanced Parkinson's disease. Aymard, N; Rondot, P; Teinturier, A; Ziegler, M, 1989)	0.55
" The optimal therapeutic dosage of Sinemet CR was equal to that of Madopar HBS but 12% higher than that of standard Madopar."	( Treatment of early Parkinson's disease with controlled-release levodopa preparations. Rinne, JO; Rinne, UK, 1989)	0.52
" The mean daily dosage of levodopa was 662."	( Sinemet CR in the treatment of patients with Parkinson's disease already on long-term treatment with levodopa. Aarli, JA; Gilhus, NE, 1989)	0.79
" For optimal results, a higher dosage is needed (mean = 33%), but the number of doses per day can be reduced (mean = 30%)."	( Experiences with Sinemet CR in the Paracelsus-Elena-Klinik. Gerdes, U; Haagen, K; Ulm, G, 1989)	0.28
" Daily "on" time, dyskinesia time, disability score, levodopa dosage requirement, and dosing frequency on Sinemet CR were compared with baseline values on standard Sinemet therapy."	( Long-term clinical efficacy of Sinemet CR in patients with Parkinson's disease. Dickins, QS; Dobson, J; Rodnitzky, RL, 1989)	0.53
" For the control of PDFR most important thing was the reduction of dosage of levodopa."	( [Clinical characteristics of painful dystonic foot response in patients with Parkinson's disease]. Hara, H; Kawase, J; Wakayama, Y, 1989)	0.51
" The dose-response curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA."	( NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. Iversen, SD; Miyaji, M; Naruse, T; Rupniak, NM; Tye, SJ, 1989)	0.28
" The effect of NADH was dependent on the dosage and the severity of the case."	( Nicotinamidadenindinucleotide (NADH): the new approach in the therapy of Parkinson's disease. Birkmayer, GJ; Birkmayer, W, )	0.13
" Although the total number of tablets and doses per day of CR-4 was reduced during the C/S period, total levodopa dosage per day was not significantly changed from either of the previous periods."	( Controlled-release carbidopa-levodopa (Sinemet) in combination with standard Sinemet in advanced Parkinson's disease. Mark, MH; Sage, JI, )	0.64
" Re-distribution of levodopa dosage which may mean smaller, more frequent doses, or larger less frequent increments, may be helpful in controlling oscillations in some patients."	( The on-off phenomenon. Lees, AJ, 1989)	0.6
"Many different formulation techniques are available for designing controlled-release dosage forms."	( Pharmaceutical design and development of a Sinemet controlled-release formulation. Dempski, RE; Oberholtzer, ER; Scholtz, EC; Yeh, KC, 1989)	0.28
" These patients required a higher total daily dosage of Sinemet CR than of Sinemet for control of parkinsonian symptoms, but less frequent dosing was required during chronic therapy."	( Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. August, TF; Bush, DF; Lasseter, KC; Musson, DG; Schwartz, S; Smith, ME; Titus, DC; Yeh, KC, 1989)	0.28
" In 19 parkinsonians with prominent dose-by-dose fluctuations, double-blind crossover trials comparing 8-week regimens of standard carbidopa/levodopa (25/100) to Sinemet CR (50/200) showed comparable clinical outcomes, with mean daily dosing for optimal control reduced from 10."	( Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. Berchou, RC; Galloway, MP; Kareti, D; Kesaree, N; LeWitt, PA; Nelson, MV; Schlick, P, 1989)	0.77
" The standard dosage forms were found to disperse soon after administration and to empty rapidly from both the fasting and the "fed" stomach."	( Gastrointestinal transit of Sinemet CR in healthy volunteers. Davis, SS; Evans, DF; Hardy, JG; Melia, CD; Short, AH; Sparrow, RA; Wilding, IR, 1989)	0.28
" Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%."	( Multicenter controlled study of Sinemet CR vs Sinemet (25/100) in advanced Parkinson's disease. Bush, DF; Hutton, JT; Liss, CL; Morris, JL; Reines, S; Smith, ME, 1989)	0.51
" With continuous levodopa treatment, however, the threshold for dyskinesias begins to rise and the dose-response relation shifts to the right; clinically, the severity of both dyskinesias and on-off fluctuations tends to diminish."	( Rationale for continuous dopaminomimetic therapy of Parkinson's disease. Baronti, F; Chase, TN; Fabbrini, G; Heuser, IJ; Juncos, JL; Mouradian, MM, 1989)	0.62
" Total levodopa dosage was not significantly changed over the year."	( Long-term efficacy of controlled-release carbidopa/levodopa in patients with advanced Parkinson's disease. Mark, MH; Sage, JI, )	0.84
" No serious side effects were found within the therapeutic dosage of 50-225mg/day The results showed that L-SPD is a new type of anti-dyskinesia agent deserving further pharmacological investigation."	( [Clinical study on the treatment of dyskinesia by L-stepholidine]. Le, W, 1989)	0.28
" Memory scores were correlated with age, sex, education, marital status, length of illness, age at onset of illness, dosage and time on medication, functional status, and the major symptoms of parkinsonism."	( Correlates of memory in Parkinson's disease. Reynolds, CM; Riklan, M; Stellar, S, 1989)	0.28
" The effects of L-Dopa dosage adjustments after hospitalization were particularly considered."	( [The problems of L-dopa therapy in the course of Parkinson syndrome]. Emskötter, T; Heidenreich, C; Lachenmayer, L, 1989)	0.28
" Only in 11% of cases, an augmentation of the dopa medication was found to be effective in improving the clinical syndrome, whereas in 43%, a substantial reduction of dosage was necessary and resulted in a marked improvement of the clinical syndrome."	( [The problems of L-dopa therapy in the course of Parkinson syndrome]. Emskötter, T; Heidenreich, C; Lachenmayer, L, 1989)	0.28
" Plasma ALAAD 2 hours after dosing was normal in Groups I and II."	( Induction of aromatic-L-amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism. Boomsma, F; Hovestadt, A; Man in 't Veld, AJ; Meerwaldt, JD; Schalekamp, MA, 1989)	0.28
" The total daily dose of L-DOPA was not significantly changed, but dosing frequency was almost halved."	( An open trial of controlled release carbidopa/L-dopa (sinemet CR) for the treatment of mild-to-moderate Parkinson's disease. Friedman, JH; Lannon, MC, 1989)	0.28
" When the dose-response curves to different dosages of L-DOPA were examined in normal rats without striatal lesions, it was found to exhibit a steeper rise than that of DA."	( Effect of exogenous L-dopa on behavior in the rat: an in vivo voltammetric study. Akiyama, A; Nakazato, T, 1989)	0.28
" Regardless of hormonal treatment condition, a clear dose-response increase in DA and 3,4-dihydroxyphenylacetic acid (DOPAC), but not 5-HIAA, output was observed in response to the increasing doses of L-DOPA infusion."	( Progesterone enhances L-dopa-stimulated dopamine release from the caudate nucleus of freely behaving ovariectomized-estrogen-primed rats. Dluzen, DE; Ramirez, VD, 1989)	0.28
" In this study, the acute dose-response profile of intravenously administered levodopa for both inducing dyskinesia and alleviating parkinsonism, and its duration of action on these motor manifestations were evaluated in 52 parkinsonian patients."	( Pathogenesis of dyskinesias in Parkinson's disease. Baronti, F; Chase, TN; Fabbrini, G; Heuser, IJ; Juncos, JL; Mouradian, MM, 1989)	0.51
" For remoxipride, the dose-response curve for antagonism of GBL-reversal was superimposable over that for antagonism of apomorphine-induced stereotypies, with an ED50 value about 12 times higher than that for antagonism of apomorphine-induced hyperactivity."	( Comparison of the effects of haloperidol, remoxipride and raclopride on "pre"- and postsynaptic dopamine receptors in the rat brain. Fowler, CJ; Magnusson, O; Mohringe, B; Ogren, SO; Wijkström, A, 1988)	0.27
" The model is then used to optimize the dosage regimen for each patient individually (according to the clinical particularities and needs of each patient) with respect to an objective function which includes the symptoms dynamically and the total amount of levodopa which is to be administered."	( Optimization of symptomatic therapy in Parkinson's disease. Albani, C; Hacisalihzade, SS; Mansour, M, 1989)	0.46
" Levodopa dosage ranged from 300 to 687 mg/day and was kept stable throughout the study."	( Treatment of Parkinson's disease with subcutaneous lisuride infusions. Fernandez Pardal, M; Gatto, M; Micheli, F; Perez y Gonzalez, N, 1988)	1.19
" Even better results could be accomplished in an extended trial attempting to establish the best dosage ratio of the combination, possibly admitting increased dosage."	( A combined regimen of subcutaneous lisuride and oral Madopar HBS in Parkinson's disease. Aljanati, R; Caamaño, JL; Chouza, C; de Medina, O; Romero, S; Scaramelli, A, 1988)	0.27
" Administration in daily dosage of 10 mgs produces an almost complete inhibition of the enzyme."	( R-(-)-deprenyl and parkinsonism. Yahr, MD, 1987)	0.27
"The pathogenesis of "random" fluctuations in parkinsonian mobility, which are not clearly related to the dosing schedule of levodopa, has not been determined."	( Erratic gastric emptying of levodopa may cause "random" fluctuations of parkinsonian mobility. Kurlan, R; Lichter, D; Miller, C; Nutt, JG; Rothfield, KP; Shoulson, I; Woodward, WR, 1988)	0.78
" Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group."	( Deprenyl in the treatment of symptom fluctuations in advanced Parkinson's disease. Ahlskog, JE; Duvoisin, RC; Foo, SH; Golbe, LI; Gopinathan, G; Lieberman, AN; Muenter, MD; Neophytides, AN, 1988)	0.27
" Pergolide in doses of 2 mg per day considerably and durably improved the parkinsonian symptoms and enabled the patients to reduce L-dopa dosage by about 50%."	( [Clinical study of pergolide in Parkinson's disease]. Delwaide, PJ; Gonce, M, 1985)	0.27
" These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests."	( Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia. Balsamo, A; Cacciari, E; Cau, M; Cicognani, A; Paolucci, G; Pirazzoli, P; Rosito, P; Tosi, MT; Vecchi, V, 1988)	0.27
" The antiparkinsonian threshold dose correlated best with duration of symptoms; the dyskinesia threshold dose, therapeutic window, and dose-response slope related most closely with the duration of levodopa treatment."	( Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part II. Bartko, JJ; Chase, TN; Fabbrini, G; Juncos, JL; Mouradian, MM; Schlegel, J, 1988)	0.46
" The following report concerns a 62-year-old female Parkinsonian patient with levodopa-induced "On-Off", depression and sleep disturbances, the severity of which was dramatically reduced by administration of low dosage amitriptyline (a serotonergic agent)."	( Serotonergic mechanisms in levodopa-induced "on-off" and sleep disorders in Parkinson's disease. Sandyk, R, 1988)	0.8
" Reduced dosage frequency and significant motor improvement with reduced fluctuation occurred and were maintained with CR4-Sinemet compared with baseline on Sinemet."	( Controlled-release carbidopa/levodopa (CR4-Sinemet) in Parkinson's disease patients with and without motor fluctuations. Carroll, VS; Carvey, PM; Gilley, D; Goetz, CG; Klawans, HL; Shannon, KM; Tanner, CM, 1988)	0.57
" During the first month the dosage titration was aimed at finding the optimal therapeutic effect."	( Clinical trial of Madopar HBS in parkinsonian patients with fluctuating drug response after long-term levodopa therapy. Aymard, N; Holzer, J; Rondot, P; Ziegler, M, 1987)	0.49
"Madopar HBS (125 mg) is a controlled-release dosage form with 100 mg L-dopa and 25 mg benserazide."	( The hydrodynamically balanced system: a novel principle of controlled drug release. Erni, W; Held, K, 1987)	0.27
" At the beginning the patients were switched from standard Madopar to Madopar HBS, initially keeping constant L-dopa dosage and the number of daily doses."	( Open clinical study of Madopar HBS. Ludin, HP, 1987)	0.27
" However, with the new formulation the dosage had to be increased by 86% on average as compared with standard Madopar."	( Treatment of parkinsonian conditions with a controlled-release form of levodopa--preliminary study. D'Andrea, G; Durisotti, C; Ferro-Milone, F; Lion, P; Lorizio, A; Nordera, GP, 1987)	0.51
" For the first few days (up to 1 week) dosage and number of daily intakes of HBS were the same as those of the standard formulation."	( Preliminary experience with Madopar HBS: clinical observations and plasma levodopa concentrations. Baas, H; Fischer, PA, 1987)	0.5
" The overall increase in dosage of levodopa with Madopar HBS was 54% in comparison with the initial standard Madopar dosage."	( Open multicenter trial with Madopar HBS in parkinsonian patients. Preliminary assessment after short-term treatment. Heersema, T; Jansen, EN; Meerwaldt, JD; Speelman, JD; van Manen, J, 1987)	0.55
" The frequency of drug intake was unaltered but daily dosage could be increased by 30% without increasing severity of abnormal movements to a similar degree."	( [Controlled release levodopa-benserazide and changes in efficacy during treatment of Parkinson's disease]. Aymard, N; Holzer, J; Rondot, P; Ziegler, M, 1987)	0.6
") age 80(5) years, showed that nocturnal dosing with levodopa produced a clinically significant improvement in sleep both as assessed subjectively and by measurement of number of spontaneous moves in bed."	( Parkinson's disease in the elderly: response to and optimal spacing of night time dosing with levodopa. Denham, MJ; Deshmukh, AA; Dobbs, RJ; Dobbs, SM; Leeman, AL; Nicholson, PW; O'Neill, CJ; Royston, JP, 1987)	0.74
" In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS."	( Madopar HBS in Parkinson patients with nocturnal akinesia. Jansen, EN; Meerwaldt, JD, 1988)	0.27
" It may improve even those patients with fluctuations who have failed to obtain optimal benefit from all forms of manipulation of the dosage schedule of levodopa or the addition of newer ancillary medications."	( Practical application of a low-protein diet for Parkinson's disease. Lang, AE; Riley, D, 1988)	0.47
" Daily dosage frequency was significantly reduced with SINEMET CR compared with SINEMET 25/100, while the daily amount of levodopa required with SINEMET CR was significantly greater."	( Treatment of chronic Parkinson's disease with controlled-release carbidopa/levodopa. Elias, JW; Hutton, JT; Imke, SC; Morris, JL; Román, GC, 1988)	0.71
"Dopamine (DA) has rarely been administered at low dosage to stable patients with pulmonary hypertension (PAH) secondary to chronic obstructive lung disease (COLD)."	( Hemodynamic effects of a single dose of dopamine and L-dopa in pulmonary hypertension secondary to chronic obstructive lung disease. Arnaud, A; Philip-Joet, F; Saadjian, A; Tran Guyen, A; Vestri, R, 1988)	0.27
" Although the bioavailability after oral dosing is reduced as compared with standard Madopar (60-70%), this difference seems to be due to incomplete absorption rather than altered disposition of the drug."	( Single-dose pharmacokinetics of Madopar HBS in patients and effect of food and antacid on the absorption of Madopar HBS in volunteers. Allen, JG; Bird, H; Malcolm, SL; Marion, MH; Marsden, CD; O'Leary, CG; Quinn, NP, 1987)	0.27
" At the end of the dosage adaptation phase (9 weeks) most patients improved; in patients with 'on-off' phenomenon, parkinsonism became less severe, on periods were longer, and fluctuations decrease; end-of-dose impairment resolved in 4 patients."	( Substitution of standard Madopar by Madopar HBS in parkinsonians with fluctuations. Aljanati, R; Caamano, JL; Chouza, C; de Medina, O; Gonzales Panizza, V; Romero, S; Scarmelli, A, 1987)	0.27
" The dosage was adjusted until optimal response was obtained."	( Madopar HBS: slow-release levodopa and benserazide in parkinsonian patients presenting marked fluctuations in symptoms on standard L-dopa treatment. Dupont, E; Hansen, E; Jensen, NO; Mikkelsen, B; Mikkelsen, BO, 1987)	0.57
" In all patients of the first group, after 3 months on stable 'optimal' dosage schedule, the previous L-dopa treatment was abruptly replaced, dose for dose, from one day to another by Madopar HBS, a new controlled-release form of Madopar."	( Therapeutic value of Madopar HBS: judgment after 2 years experience. Siegfried, J, 1987)	0.27
" The method has been adopted official first action for determination of the active ingredients in levodopa tablets and capsules and in levodopa-carbidopa tablets and for content uniformity testing in the combination dosage form."	( Liquid chromatographic determination of levodopa and levodopa-carbidopa in solid dosage forms: collaborative study. Ting, S, )	0.62
" The dosage of L-dopa infusion ranged between 360-1,250 mg for 12 hours."	( Problems in daily motor performances in Parkinson's disease: the continuous dopaminergic stimulation. Agnoli, A; Brughitta, G; Ruggieri, S; Stocchi, F, 1986)	0.27
"Plasma 3-O-methyldopa (3OMD) concentrations in parkinsonian patients treated with levodopa on a long-term basis reflect daily levodopa dosage and do not vary markedly during the day."	( 3-O-methyldopa and the response to levodopa in Parkinson's disease. Gancher, ST; Merrick, D; Nutt, JG; Woodward, WR, 1987)	0.78
"" After the addition of bromocriptine any reductions in levodopa dosage were small, with repeated cuts made gradually over months preventing the deterioration commonly seen with larger sudden reductions in levodopa dosage."	( Bromocriptine: long-term low-dose therapy in Parkinson's disease. Bergsrud, D; Elton, RL; Racy, A; Teychenne, PF, 1986)	0.52
" In contrast, the major effect of a similar degree of irreversible blockade (86%) on the dose-response curve for the autoreceptor-selective agent EMD 23,448 was a reduction in maximal response (60% of control), indicating that EMD 23,448 is a partial agonist."	( Receptor reserve at striatal dopamine autoreceptors: implications for selectivity of dopamine agonists. Adler, CH; Bohmaker, K; Friedhoff, AJ; Goldstein, M; Helmer-Matyjek, E; Meller, E, 1986)	0.27
"In five patients with parkinsonism, the optimal dosage of a controlled-release levodopa/carbidopa preparation (CR-3) was three times higher than the dosage of Sinemet and produced higher plasma levodopa concentrations, but did not reduce the fluctuations in plasma levodopa or clinical response."	( Clinical and biochemical studies with controlled-release levodopa/carbidopa. Carter, JH; Nutt, JG; Woodward, WR, 1986)	0.74
" In the sixth year, it appeared necessary to increase the dosage in the first three groups."	( Low-dosage treatment in de novo patients with Parkinson's disease: a prospective study. van der Drift, JH, 1987)	0.27
" CI 201-678 demonstrated a good effect against rigidity, impairment of gait and posture, as well as impaired self-care, although daily levodopa dosage was concomitantly reduced."	( Therapeutic experiences with an abeorphine derivative in Parkinson's disease. Birbamer, G; Gerstenbrand, F; Poewe, W; Ransmayr, G, 1987)	0.48
" Eight patients required a 41% reduction in total L-dopa dosage and discontinuation of all adjuvant therapy to reduce the preponderance of chorea."	( Influence of dietary protein on motor fluctuations in Parkinson's disease. Barry, K; Pincus, JH, 1987)	0.27
"A system theoretical approach to the general multiple dosing problem is discussed [1], which is in turn reduced to a classical parameter optimization problem."	( A simple algorithm for the solution of the multiple dosing problem. Hacisalihzade, SS, 1985)	0.27
" A 37% improvement of the mean neurologic deficit score was obtained at the maximal daily dosage of 20 mg."	( Low dosages of bromocriptine added to levodopa in Parkinson's disease. Elton, RL; Hoehn, MM, 1985)	0.54
" In four HNB cell lines the dopamine antagonists domperidone, pimozide, and spiroperidol inhibited macromolecular synthesis in vitro as indicated by decreased 3H-TdR and 14C-leu incorporation in a dose-response fashion with at least 50% inhibition noted at 10(-6)M concentration of each drug."	( Inhibition of human neuroblastoma by dopamine antagonists. McGrath, PC; Neifeld, JP, 1985)	0.27
" Levodopa combined with a peripheral decarboxylase inhibitor is the treatment of choice thereafter, and with the appearance of fluctuations it is necessary to increase the frequency of dosage of levodopa and to consider adding bromocriptine."	( The treatment of Parkinson's disease. Morris, JG, 1985)	1.18
" The dosage of drug was titrated at each visit to give minimum risk with acceptable benefit."	( Patient benefits of l-dopa and a decarboxylase inhibitor in the treatment of Parkinson's disease in elderly patients. Admani, AK; Cordingley, GJ; Harris, RI; Verma, S, 1985)	0.27
" We describe five patients in whom an apparent psychologic effect from levodopa prompted dosage escalation to the point of toxicity."	( Sinemet "abusers". Nausieda, PA, 1985)	0.5
" Complete remission of symptoms was obtained with low dosage of L-dopa."	( Idiopathic fluctuating dystonia: a case of foot dystonia and writer's cramp responsive to L-dopa. Deonna, T; Ferreira, A, 1985)	0.27
"A new dosage form of levodopa, which has the characteristics of loading high concentrations of levodopa at the upper part of the intestine, has been developed to improve its bioavailability."	( Dosage form design for improvement of bioavailability of levodopa VI: formulation of effervescent enteric-coated tablets. Arai, M; Ikegami, Y; Morioka, T; Nakajima, E; Nishimura, K; Nitanai, T; Sasahara, K, 1984)	0.83
" In some subjects it is difficult to establish a clear relation between levodopa dosage and timing and the resultant clinical effects."	( Complicated response fluctuations in Parkinson's disease: response to intravenous infusion of levodopa. Marsden, CD; Parkes, JD; Quinn, N, 1982)	0.72
" Subsequently they were treated with either a mean dosage of 444 mg levodopa and benserazide (47 patients) or a combination of a mean of 298 mg levodopa and benserazide plus 17 mg bromocriptine (32 patients)."	( [Combined treatment of the early stages of Parkinson's syndrome with bromocriptine and levodopa. The results of a multicenter study]. Fischer, PA; Majer, M; Przuntek, H; Welzel, D, 1984)	0.73
" Following effective stereotaxic surgery, drug therapy should be continued with reduced dosage of the drugs."	( [Combined (surgical and drug) therapy of parkinsonism]. Iadgarov, IS; Kandel', EI, 1984)	0.27
" Alternate-day therapy results in less cumulative dosage and may better preserve existing compensatory striatal activity."	( Intermittent levodopa therapy in parkinsonism. Koller, WC, 1983)	0.64
"The purpose of this double-blind placebo controlled study was to estimate how much the levodopa dosage can be reduced, when deprenyl is used, without worsening the disease and to see whether deprenyl can reduce the "off-periods"."	( Deprenyl (selegiline) combined with levodopa and a decarboxylase inhibitor in the treatment of Parkinson's disease. Hajba, A; Presthus, J, 1983)	0.76
" We suggest that the analysis of the blink reflex after a single oral levodopa-carbidopa dosage could provide an objective and quantifiable method for the detection of individuals at risk for Huntington's disease."	( Early detection of Huntington's disease. Blink reflex and levodopa load in presymptomatic and incipient subjects. Esteban, A; Giménez-Roldán, S; Mateo, D, 1981)	0.74
" Reducing the dosage prevents dyskinesia."	( [Toxic drug effects of antiparkinson therapy and their preventability]. Danielczyk, W, )	0.13
" The observed duration of action and dose-response properties of carbidopa suggested that current empirically based dose schedules are optimal and supported the concept that decarboxylase inhibitors enhance the clinical effect of L-dopa largely by reducing the extent of first-pass metabolism rather than through an action on the decarboxylase enzyme in cerebral capillaries."	( L-dopa decarboxylation in chronically treated patients. Calne, DB; Kopin, IJ; Trombley, IK; Ward, CD, 1984)	0.27
" Fatal hyperpyrexia followed simultaneous levodopa withdrawal and a decrease in the dosage of diphenhydramine."	( Fatal hyperpyrexia after withdrawal of levodopa. Mutani, R; Sechi, GP; Tanda, F, 1984)	0.8
" From our observations, low dosage of levodopa is a desirable alternative, but not the answer to therapeutic failure."	( Chronic low-dose levodopa therapy in Parkinson's disease: an argument for delaying levodopa therapy. Laverty, WH; Rajput, AH; Stern, W, 1984)	0.88
" Also, using as low a dosage as possible should reduce the risk of any long-term complication related to accumulative dose."	( Should levodopa therapy for Parkinsonism be started early or late? Evidence against early treatment. Bressman, SB; Fahn, S, 1984)	0.72
" It is concluded that agonist induction of subsensitivity in the DA system is difficult to reproduce and may depend on highly specific dosage conditions and treatment schedules."	( The effect of chronic bromocriptine and L-dopa on spiperone binding and apomorphine-induced stereotypy. Bannet, J; Belmaker, RH; Globus, M; Lerer, B, 1982)	0.26
" Interactions at the absorption level can be avoided by administering the antacid one hour after intake of the other drugs (one hour after meals) which is also the optimum dosing schedule to ensure good antacid effect."	( [Metabolic effects of antacids and interactions with other drugs]. Gugler, R; Musch, E, 1983)	0.27
" As the reason for the weak effectiveness of alpha-methyldopa on the incidence of AIHA, it might be considered that the dosage employed was not sufficiently high enough and/or it may be due to the species difference between man and animals."	( Influence of carbidopa, an aromatic amino acid decarboxylase inhibitor, on the development of autoimmune hemolytic anemia in NZB mice. Kemi, M; Kondo, M; Maki, E; Tanabe, K, 1983)	0.27
" Increased absorption of a given dose of levodopa in the elderly explains in part the lower dosage requirements."	( Senile Parkinsonism and dopa pharmacokinetics. Broe, GA; Evans, MA; Triggs, EJ, 1981)	0.53
" The relation of complications to dosage is now better understood, and the ratio of dopa-decarboxylase inhibitor to levodopa inhibitor to levodopa of 1:4 is better than the previous 1:10."	( Sinemet and the treatment of Parkinsonism. Boshes, B, 1981)	0.47
" The very melanotic F1 cell line showed no inhibition by dopa or dopamine, but pimozide inhibited 14C-leu and 3H-TdR incorporation in a dose-response fashion; 50% inhibition was noted at 10(-9) M concentration with no loss in cell viability as tested by trypan blue exclusion or cell counting."	( Effects of dopamine agonists and antagonists on murine melanoma: correlation with dopamine binding activity. Krummel, TM; Neifeld, JP; Taub, RN, 1982)	0.26
" PRL increase after benserazide was compared with PRL response after carbidopa at the same dosage in untreated parkinsonian patients."	( Prolactin response to acute administration of different L-dopa plus decarboxylase inhibitors in Parkinson's disease. Agnoli, A; Baldassarre, M; D'Urso, R; De Giorgio, G; Falaschi, P; Rocco, A; Ruggieri, S, 1982)	0.26
" The daily dose of levodopa should be as low as possible and when dyskinesias develop, the dosage of both levodopa and anticholinergic agents should be reduced."	( Management of motor side effects of chronic levodopa therapy. Jankovic, J, 1982)	0.85
" Therapeutic intervention with dosage adjustments and/or drug holidays are indicated when psychosis occurs."	( Behavioral alterations and the therapy of parkinsonism. Klawans, HL, 1982)	0.26
" The lowering of epinephrine concentration was greater with L-dopa than with D-dopa, was dose-related over a dosage range of 50 to 200 mg/kg of L-dopa and was not prevented by a dopamine receptor antagonist."	( Effects of L-dopa on epinephrine concentration in rat brain: possible role of inhibition of norepinephrine N-methyltransferase by S-adenosylhomocysteine. Fuller, RW; Hemrick-Luecke, SK; Perry, KW, 1982)	0.26
" These findings constitute biochemical evidence for selective elevation of brain DA during the first postnatal week of life after L-DOPA administration in a dosage that is also capable of enhancing the coordination required for swimming behavior."	( Brain catecholamine concentration during the first week of development in rats. Korányi, L; Phelps, CP; Tamásy, V, 1982)	0.26
" In contrast, there seemed to be a correlation between dopamine turnover and optimum dosage of l-DOPA."	( [Value of the probenecid test in the diagnosis and treatment of parkinson disease]. Mendlewicz, J; Noel, G; Vanderheyden, JE, )	0.13
" Because most patients required lower dosage after the holiday, dyskinesias were no longer present."	( Drug holiday and management of Parkinson disease. Klawans, HL; Koller, WC; Nausieda, PA; Perlik, S; Weiner, WJ, 1980)	0.26
" Combination of the two drugs permitted rapid increase in bromocriptine dosage from 22."	( Bromocriptine and domperidone in the treatment of Parkinson disease. Agid, Y; Illas, A; Lhermitte, F; Quinn, N, 1981)	0.26
" The use of minimum dosage has therefore been recommended."	( Alternate day levodopa therapy in parkinsonism. Koller, WC, 1982)	0.62
" A low initial dose (1 mg per day) and slow escalation in dosage produced an optimal, though delayed improvement."	( Bromocriptine: low-dose therapy in Parkinson disease. Bergsrud, D; Elton, RL; Racy, A; Teychenne, PF; Vern, B, 1982)	0.26
" Patients were maintained on a stable, therapeutically optimal dosage and schedule of levadopa-carbidopa (Sinemet) throughout the study."	( Parkinson's disease: Cogentin with Sinemet, a better response. Gilden, ER; Hansch, EC; Hirsch, SB; Potvin, AR; Potvin, JH; Syndulko, K; Tourtellotte, WW, 1982)	0.26
" This methylamphetamine treatment also attenuated the ability of methylamphetamine and apomorphine to produce increases in locomotor activity without shifting the dose-response curve to the right or left."	( The effects of dopaminergic agents on the locomotor activity of rats after high doses of methylamphetamine. Lucot, JB; Schuster, CR; Seiden, LS; Wagner, GC, 1980)	0.26
" However, in both dogs and patients, the relationship after oral dosing was nonlinear, with the relative AUC increasing with increasing dose."	( Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on pharmacokinetic behavior of levodopa in dogs and Parkinsonian patients. Habara, T; Morioka, T; Nakajima, E; Nitanai, T; Sasahara, K, 1980)	0.51
" End-of-dose deterioration ('wearing-off' effect of individual doses) occurred in 65 per cent of patients: unpredictable oscillations in motor performance (the 'on-off' phenomenon) unrelated to the time and dosage of levodopa, occurred in 10 per cent."	( The impact of treatment with levodopa on Parkinson's disease. Lees, AJ; Shaw, KM; Stern, GM, 1980)	0.74
" Two dosage strengths are available: 100 mg levodopa plus 25 mg benserazide and 50 mg levodopa plus 12."	( [Benefits of a new galenic form of levodopa and benserazide in the treatment of patients with Parkinson disease]. Dessibourg, CA; Gachoud, JP, 1995)	0.83
" In the present study, we investigated the effect of increased dosage and duration of levodopa on amblyopes' visual functions."	( Visual acuities and scotomas after 3 weeks' levodopa administration in adult amblyopia. Gottlob, I; Reinecke, RD; Wizov, SS, 1995)	0.78
" However, increasing the dosage and the duration of levodopa did not enhance the effect in adults."	( Visual acuities and scotomas after 3 weeks' levodopa administration in adult amblyopia. Gottlob, I; Reinecke, RD; Wizov, SS, 1995)	0.8
"Efficacy of apomorphine following subcutaneous, rectal, sublingual, and intranasal dosage forms are evaluated."	( Apomorphine for motor fluctuations and freezing in Parkinson's disease. Corboy, DL; Sage, JI; Wagner, ML, 1995)	0.29
" The IDI schedule that produced a satisfactory LDR was specific for each patient, since longer DIs failed to produce the required LDR, and a shorter IDI schedule (resulting in larger cumulative dosage of levodopa) did not significantly enhance the response."	( The subacute levodopa test for evaluating long-duration response in Parkinson's disease. Aguglia, U; Branca, D; Colao, R; Montesanti, R; Nicoletti, G; Palmieri, A; Parlato, G; Quattrone, A; Rizzo, M; Zappia, M, 1995)	0.85
" We conclude that mood and anxiety fluctuations related to levodopa dosing are robust pharmacologic, and not placebo, effects."	( Dose-response relationship of levodopa with mood and anxiety in fluctuating Parkinson's disease: a double-blind, placebo-controlled study. Carter, JH; Maricle, RA; Nutt, JG; Valentine, RJ, 1995)	0.82
" Regular dosing with levodopa or apomorphine reliably resulted in peak-dose dyskinesia which was scored in terms of its choreic and dystonic components."	( Thalamotomy for the alleviation of levodopa-induced dyskinesia: experimental studies in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated parkinsonian monkey. Crossman, AR; Page, RD; Sambrook, MA, 1993)	0.88
" To provide an overview for physicians and patients on the diversity of preparations available in the different countries, we compiled the most commonly used substances along with their size of dosage and formula in an international guide to drugs for PD."	( International guide to drugs for Parkinson's disease. Dodel, RC; Oertel, WH, 1995)	0.29
" Tolerance to levodopa should be considered in establishing oral dosing regimens and in developing new strategies for drug delivery."	( Effect of brief levodopa holidays on the short-duration response to levodopa: evidence for tolerance to the antiparkinsonian effects. Carter, JH; Nutt, JG; Woodward, WR, 1994)	1
" L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism."	( Suppression of dyskinesias in advanced Parkinson's disease: moderate daily clozapine doses provide long-term dyskinesia reduction. Bennett, JP; Dietrich, S; Landow, ER; Schuh, LA, 1994)	0.29
" A three times greater dosage of L-dopa-s."	( [Slow-release L-dopa vs. standard L-dopa in Parkinson patients in various stages of the disease. Studies of pharmacokinetics and motor effectiveness]. Baas, H; Bergemann, N; Fischer, PA, 1994)	0.29
" Levodopa-carbidopa in low dosage adequately controlled symptoms in most patients and delayed the appearance of dyskinesia and end of dose failure for about two years longer than conventional doses."	( The Sydney Multicentre Study of Parkinson's disease: a randomised, prospective five year study comparing low dose bromocriptine with low dose levodopa-carbidopa. Broe, GA; Hely, MA; Margrie, S; Morris, JG; O'Sullivan, DJ; Rail, D; Reid, WG; Williamson, PM, 1994)	1.4
" The relationship between apomorphine dosage and the following parameters, namely age, duration of disease, body height, body surface, skinfold thickness of the abdominal wall and the upper arm as a measure of subcutaneous fatty tissue, and amount of administered L-dopa was studied in 45 patients with Parkinson's disease in whom the apomorphine test was positive."	( [Apomorphine test in Parkinson disease--dose and corresponding parameters]. Helscher, RJ; Pinter, MM; Sattler, AP, 1993)	0.29
" The effect of levodopa in the two dosing regimens was estimated optico-electronically every 15 min and was also evaluated from videorecordings every 30 min and plasma levels of levodopa was regularly measured."	( Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson's disease. Aquilonius, SM; Bredberg, E; Johansson, K; Johnels, B; Nilsson, D; Nyström, C; Paalzow, L, 1993)	0.91
" These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens."	( Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Amantea, MA; Bravi, D; Chase, TN; Cora-Locatelli, G; Mouradian, MM; Roberts, JW, 1993)	0.74
" No addiction to the drugs, and in particular no need of a dosage increase was observed during the whole period of 18 months."	( [Restless legs syndrome. Report of experience]. Grandjean, P, 1993)	0.29
"05) after 7 days of multiple dosing with entacapone."	( Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patients. Ahtila, S; Gordin, A; Kaakkola, S; Rita, H; Teräväinen, H, 1994)	0.52
"We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa."	( Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease. Bennett, JP; Schuh, LA, 1993)	0.71
" All 10 patients had significantly decreased variability in levodopa levels permitting better titration of levodopa dosage to individual requirements."	( Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson's disease patients with 'on-off' fluctuations. Goetz, CG; Irwin, I; Kurth, MC; Langston, JW; Stebbins, GT; Tanner, CM; Tetrud, JW, 1993)	0.76
"To examine selegiline's dosing effects, we studied 16 Parkinson disease patients with motor fluctuations in a double-blind, crossover trial of selegiline at 0, 5, and 10 mg daily."	( Effects of selegiline dosing on motor fluctuations in Parkinson's disease. Hubble, JP; Koller, WC; Waters, C, 1993)	0.29
" Plasma L-dopa was evaluated in relation to dosage and postdose sampling time in 71 outpatients with Parkinson disease."	( Measuring L-dopa in plasma and urine to monitor therapy of elderly patients with Parkinson disease treated with L-dopa and a dopa decarboxylase inhibitor. Copeland, LG; Dutton, J; Playfer, JR; Roberts, NB, 1993)	0.29
" Oral LCAS allowed better titration of levodopa dosage and offered a more predictable response than LD/CD tablets."	( Oral levodopa/carbidopa solution versus tablets in Parkinson's patients with severe fluctuations: a pilot study. Irwin, I; Kurth, MC; Langston, JW; Lyness, WH; Tetrud, JW, 1993)	1.07
" Disease duration and daily levodopa dosage were similar in the three groups."	( Effect of age and disease duration on parkinsonian motor scores under levodopa therapy. Falk, M; Künig, G; Neubauer, M; Ransmayr, G; Wagner, M, 1995)	0.82
" Dosage adjustments, addition of a second medication to the drug regimen, and dietary modifications may help maximize response to symptomatic therapy."	( Moderate Parkinson's disease. Strategies for maximizing treatment. Silverstein, PM, 1996)	0.29
"To establish, in a double blind manner, the antiparkinsonian effects of repeated dosing with entacapone, a peripheral COMT inhibitor."	( Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations. Rinne, UK; Ruottinen, HM, 1996)	0.62
"The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson's disease with levodopa related fluctuations is verified."	( Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations. Rinne, UK; Ruottinen, HM, 1996)	0.86
" Titration of the dosage and additional treatment with sustained-release preparations of L-DOPA should be applied individually."	( [Therapy of idiopathic and uremic restless legs syndrome]. Oertel, WH; Stiasny, K; Trenkwalder, C, 1996)	0.29
" Whether higher doses or more frequent dosing is effective requires further investigation."	( L-DOPA/carbidopa for nocturnal movement disorders in uremia. Fine, A; Kryger, MH; Walker, SL, 1996)	0.29
" In a subsequent open-label dose-escalation phase, further improvement was documented as the dosage was gradually raised to 10 mg daily."	( Adjunctive cabergoline therapy of Parkinson's disease: comparison with placebo and assessment of dose responses and duration of effect. Adler, CH; Ahlskog, JE; Muenter, MD; Wright, KF, 1996)	0.29
" The AUC of 3-O-methyldopa decreased by 45% and AUC of homovanillic acid by 21% after 4 weeks' dosing with entacapone."	( Effect of one month's treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Rinne, UK; Ruottinen, HM, 1996)	0.49
" The first afternoon levodopa administration was substituted with an equimolar dosage of the liquid formulation levodopa methyl ester (LDME)."	( Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester. Barbato, L; Bramante, L; Nordera, G; Ruggieri, S; Stocchi, F; Vacca, L, 1996)	0.85
"Dopaminergic agonists represent an important class of drugs in Parkinson's Disease, useful: a) in delaying the beginning of L-dopa therapy; b) in supporting it, reducing its dosage and widen the therapeutic window; c) moreover, as the disease advances, in trying to treat motor fluctuations."	( Dopaminergic agonists in the treatment of Parkinson's disease: a review. Piccoli, F; Riuggeri, RM, 1995)	0.29
" The delayed levodopa absorption and lower plasma concentrations which characterise controlled-release formulations compared with standard forms must be taken into account when prescribing dosage regimens and can be complicating factors in the management of the advanced disease stages."	( Pharmacokinetic optimisation in the treatment of Parkinson's disease. Albani, F; Baruzzi, A; Contin, M; Riva, R, 1996)	0.66
" Without co-medication a high L-dopa dosage may provoke/facilitate an organic cerebral dysfunction."	( Computerised brain electrical activity findings of parkinson patients suffering from hyperkinetic side effects (hypersensitive dopamine syndrome) and a review of possible sources. Fünfgeld, EW, 1995)	0.29
" The drugs were dosed according to the individual need of the patients."	( Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients. Andersen, A; Boas, J; Boisen, E; Borgmann, R; Buch, D; Dupont, E; Helgetveit, AC; Kjaer, MO; Kristensen, TN; Mikkelsen, B; Pakkenberg, H; Presthus, J; Stien, R; Worm-Petersen, J, 1996)	0.29
"A dose-response study of the effects of entacapone on the pharmacokinetics and metabolism of levodopa and on the clinical response to levodopa was carried out in 20 parkinsonian patients with levodopa-related fluctuations."	( A double-blind pharmacokinetic and clinical dose-response study of entacapone as an adjuvant to levodopa therapy in advanced Parkinson's disease. Rinne, UK; Ruottinen, HM, 1996)	0.73
" But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinson's disease (prolongation of dosage intervals, reduction of motor fluctuations)."	( Sustained-release of levodopa: single dose study of a new formulation. Gerlach, M; Klotz, P; Kuhn, W; Müller, T; Przuntek, H, 1996)	0.61
" LDEE injections produced significant and rapid elevations of striatal levodopa, dopamine, and DOPAC, which were similar to those achieved after levodopa administration, with similar dose-response curves."	( Effect of subcutaneous administration of levodopa ethyl ester, a soluble prodrug of levodopa, on dopamine metabolism in rodent striatum: implication for treatment of Parkinson's disease. Atlas, D; Djaldetti, R; Melamed, E, 1996)	0.79
"We report a 65-year-old male parkinsonian patient who developed dominantly unilateral choreic movements over his right-side extremities after a daily dosage of up to 1,000 mg of carbidopa-levodopa (carbidopa 200 mg, levodopa 800 mg) for 12 years."	( Ventrolateral thalamotomy for dyskinesia following levodopa therapy of Parkinson's disease. Lee, ST; Lu, CS, 1996)	0.74
" Levodopa/carbidopa dosage and frequency were significantly reduced."	( Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I. Adler, CH; Chernik, DA; Dorflinger, EE; Hilaire, MS; Kurth, MC; LeWitt, P; Singer, C; Waters, C; Yoo, K, 1997)	1.47
" In the statistical investigation by the multiple analysis, the time from first onset to initiation on levodopa therapy or the duration of levodopa therapy was not closely related to the development of any adverse reaction, while Hoehn and Yahr's stage and dosage levodopa had the most significant influence on the development of adverse reactions."	( [Problems of long-term levodopa therapy in Parkinson's disease]. Nakamura, Y, 1997)	0.82
" Dosage titration occurred over the 5 years of evaluations to maintain an optimal response."	( Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson's disease. A multicenter 5-year study. The CR First Study Group. Block, G; Irr, J; Liss, C; Nibbelink, D; Reines, S, 1997)	0.53
"To determine if the combination of levodopa (LD) plus bromocriptine (Br) in the early stages of Parkinson's disease (PD) permits reduction of LD dosage and consequently results in fewer motor fluctuations and dyskinesias, a double-blind, multicenter prospective study in 50 PD patients who had responded favorably to LD while under treatment with that drug for < or = 6 months was undertaken."	( Early combination of bromocriptine and levodopa in Parkinson's disease: a prospective randomized study of two parallel groups over a total follow-up period of 44 months including an initial 8-month double-blind stage. Burguera, JA; Chacón, J; Forcadell, F; Giménez-Roldán, S; Liaño, H; Tolosa, E, 1997)	0.84
" Motor fluctuations, which slowly emerge after 3-5 years of chronic LD therapy, gradually replace the smooth pattern of response, and more frequent dosing is required."	( Problems with current pharmacologic treatment of Parkinson's disease. Hurtig, HI, 1997)	0.3
" When given in tablet form, the dosage of levodopa (which is usually combined with a decarboxylase inhibitor such as carbidopa or benserazide) often cannot be titrated adequately, and the drug may become unpredictable in its ability to relieve parkinsonian symptoms."	( Using liquid levodopa in the treatment of Parkinson's disease. A practical guide. Kurth, MC, 1997)	0.93
" Studies were performed at 5-7 days post lesion (group 1 animals), at 21 days (group 2) when denervation supersensitivity was evident by contralateral turning to apomorphine and at the same time but following 7 days dosing with LDME plus benserazide (group 3)."	( Effect of L-dopa alone and with benserazide on the spontaneous activity of striatal neurones in normal and 6-hydroxydopamine-lesioned rats. Chang, WY; Webster, RA, 1997)	0.3
" Plasma levels of levodopa, 3-O-methyldopa (3-OMD) and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined before benserazide treatment and during all benserazide dosing regimens, as existing endogenously and after administration of 250 mg levodopa."	( Pharmacodynamics of benserazide assessed by its effects on endogenous and exogenous levodopa pharmacokinetics. Crevoisier, C; Dingemanse, J; Kleinbloesem, CH; Wood, ND; Zürcher, G, 1997)	0.86
" As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients."	( Long-duration response to levodopa influences the pharmacodynamics of short-duration response in Parkinson's disease. Aguglia, U; Colao, R; Gambardella, A; Montesanti, R; Oliveri, RL; Quattrone, A; Rizzo, M; Zappia, M, 1997)	0.83
" Compound 6, 3-benzyl-8-methyl-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one, increased DOPA (L-3,4-dihydroxyphenylalanine) synthesis 84% in the hippocampus and 10% in the striatum of rat brain when dosed orally at 10 mg/kg."	( Chromeno[3,4-c]pyridin-5-ones: selective human dopamine D4 receptor antagonists as potential antipsychotic agents. Capiris, T; Connor, DT; Heffner, TG; MacKenzie, RG; Miller, SR; Pugsley, TA; Unangst, PC; Wise, LD, 1997)	0.3
" In most cases the dosage of levodopa should be lowered or stopped altogether."	( [Psychiatric complications of L-dopa: physiopathology and treatment]. Castro-García, A, 1997)	0.59
" Used as adjuvant treatment to levodopa, they help lowering the dosage of levodopa."	( [Initial treatment of Parkinson's disease]. Kulisevsky, J; López-Villegas, D, 1997)	0.58
" At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase."	( Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group. Bailey, P; Deptula, D; Dorflinger, E; Kurth, M; LeWitt, P; Pedder, S; Shulman, LM; Waters, CH, 1997)	0.55
" To establish the dose-response profile for the dyskinesiogenic effect of LD, we administered intravenous LD over a wide dose range to 25 patients with advanced PD."	( Effects of supra-threshold levodopa doses on dyskinesias in advanced Parkinson's disease. Blanchet, P; Chase, TN; Klaassen, AA; Metman, LV; Mouradian, MM; van den Munckhof, P, 1997)	0.59
"Two patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms."	( Levodopa dependence and abuse in Parkinson's disease. Spigset, O; von Schéele, C, )	1.81
" In the first study (de novo patients), cabergoline was administered at increasing dosages until the maximum dosage of 2 mg/day once a day for 8 weeks; subsequently L-dopa (250 mg/day) was added."	( Clinical and pharmacokinetic evaluation of L-dopa and cabergoline cotreatment in Parkinson's disease. Bonuccelli, U; Colzi, A; Del Dotto, P; Fariello, R; Musatti, E; Persiani, S; Strolin Benedetti, M, 1997)	0.3
" dosing with the lowest fully effective dose of apomorphine (averaging 27."	( Motor response to a dopamine D3 receptor preferring agonist compared to apomorphine in levodopa-primed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys. Blanchet, PJ; Chase, TN; Konitsiotis, S, 1997)	0.52
" As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened."	( Clinical implications of sustained dopaminergic stimulation. Barbato, L; Berardelli, A; Bonamartini, A; Manfredi, M; Patsalos, PN; Ruggieri, S; Stocchi, F, 1994)	0.62
" In the statistical investigation by the multivariate analysis (quantification method type II), the age of initial levodopa therapy, the duration from the onset to the initiation of levodopa therapy, and the duration of levodopa therapy were not closely related to the development of any adverse reaction, while Hoehn & Yahr's stage and the dosage of levodopa had the most significant influence on the development of adverse reactions."	( [Multivariate analysis of the problems of long-term levodopa therapy in Parkinson's disease]. Endo, S; Hikiji, A; Nakamura, Y; Yoshinaga, J, 1997)	0.76
" The mean daily levodopa dosage was 569 mg for Std-L compared with 751 mg for L-CR."	( Comparison of standard carbidopa-levodopa and sustained-release carbidopa-levodopa in Parkinson's disease: pharmacokinetic and quality-of-life measures. Koller, WC; Lyons, K; McGuire, D; Pahwa, R; Robischon, M; Silverstein, P; Zwiebel, F, 1997)	0.92
" These results indicate that the mode of administration of a D2 dopamine receptor agonist, such as U91356A, although at a roughly equivalent dosage influences the extent of inhibition of the expression of PPE in the denervated striatum of monkeys."	( Preproenkephalin mRNA expression in the caudate-putamen of MPTP monkeys after chronic treatment with the D2 agonist U91356A in continuous or intermittent mode of administration: comparison with L-DOPA therapy. Bédard, PJ; Blanchet, PJ; Calon, F; Di Paolo, T; Goulet, M; Morissette, M; Soghomonian, JJ, 1997)	0.3
" However, no correlation was found between delta BW, delta BMI or %Fat on the one hand, and the disease severity or the total dosage of L-dopa with carbidopa on the other."	( [Body fat loss in patients with Parkinson's disease]. Sakajiri, K; Takamori, M, 1997)	0.3
"The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage."	( Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson's Disease Study Group II (TIPS II). Burgunder, JM; Dorflinger, E; Dupont, E; Findley, LJ; Olsson, JE, 1997)	0.85
" Across groups, mean Hoehn and Yahr stage and daily levodopa dosage progressively increase (and mean Schwab and England disability ratings decrease), but more conservatively than in prior reports in the postlevodopa era."	( Motor complications of chronic levodopa therapy in Parkinson's disease. Busenbark, K; Hubble, J; Koller, WC; Lyons, K; McGuire, D; Michalek, D; Miyawaki, E; Pahwa, R; Smith, D; Tröster, AI, 1997)	0.83
""Freezing" is a sudden, unforeseen state of immobility occurring independently of L-Dopa dosage timing and often presents in connection with walking, speech and hand movements."	( [Freezing phenomenon in Parkinson disease]. Ringendahl, H; Sierla, T, 1997)	0.3
" Thus, with increasing degeneration of the nigrostriatal system, swings in plasma levodopa concentrations associated with standard dosage regimens produce nonphysiological fluctuations in intrasynaptic dopamine."	( The significance of continuous dopaminergic stimulation in the treatment of Parkinson's disease. Chase, TN, 1998)	0.53
"5 mg/day) achieved a statistically significant decrease in levodopa dosage compared with placebo (18 vs 3%) and improved the Unified Parkinson's Disease Rating Scale scores for activities of daily living in a greater number of patients (23 vs 4%)."	( Clinical experience with cabergoline in patients with advanced Parkinson's disease treated with levodopa. Marsden, CD, 1998)	0.76
" DOPA ester 300 ng, microinjected 1 min previously, shifted a dose-response curve for DOPA 30-300 ng to the right without reduction of the maximum response, showing a competitive mode of antagonism."	( [Studies on novel, stable and potent competitive antagonists against L-DOPA]. Furukawa, N; Goshima, Y; Misu, Y; Miyamae, T; Okumura, Y; Shimizu, M; Sugiyama, Y, 1997)	0.3
" However, in the long term, the reduction of levodopa dosage in the STN group led to an indirect reduction of LID similar to that in the GPi group during activities of everyday life."	( Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease. Benabid, AL; Benazzouz, A; Hoffmann, D; Krack, P; Limousin, P; Pollak, P; Xie, J, 1998)	0.56
" Tolcapone can significantly reduce the off time and increases the total on time while simultaneously reducing levodopa dosage and frequency."	( [Tolcapone: a different, effective approach to improving dopaminergic treatment in Parkinson's disease]. Kulisevsky, J, 1998)	0.51
" Despite a clear, asymmetric improvement of cardinal Parkinson's disease symptoms after unilateral PVP, changes in the dose-response L-dopa profile occurred symmetrically, suggesting that mechanisms underlying the two effects are distinct."	( Changes in the motor response to acute L-dopa challenge after unilateral microelectrode-guided posteroventral pallidotomy. Cammarotta, A; Leiguarda, R; Merello, M; Nouzeilles, MI; Pikielny, R, )	0.13
" The great increase in levodopa responses by deprenyl suggests a likely therapeutic use of this dopamine precursor with a higher dosage of the MAO inhibitor, to reduce effectively the daily levodopa requirements in Parkinson's disease patients."	( Modification of levodopa responses by deprenyl (selegiline): an electrophysiological and behavioral study in the rat relevant to Parkinson's disease. Bernardi, G; Bonci, A; Federici, M; Mercuri, NB; Scarponi, M; Siniscalchi, A, 1998)	0.96
" Dosing days were separated by a 7-day washout."	( The effect of tolcapone on levodopa pharmacokinetics is independent of levodopa/carbidopa formulation. Aitken, J; Fotteler, B; Jorga, K; Nielsen, T; Sedek, G, 1998)	0.6
" Daily levodopa dosage requirements decreased significantly."	( Highlights of the North American and European experiences. Goetz, CG, 1998)	0.76
" At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase."	( Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. Tolcapone Stable Study Group. Bailey, P; Deptula, D; Dorflinger, E; Kurth, M; LeWitt, P; Pedder, S; Shulman, LM; Waters, CH, 1998)	0.55
"In an open study, a group of 10 PD patients was treated with low dosage clozapine (mean 30 mg/day) for a 4-month period and L-dopa dyskinesias were evaluated in basal conditions and during clozapine treatment after the usual morning dose of clozapine."	( Low dosage clozapine effects on L-dopa induced dyskinesias in parkinsonian patients. Adipietro, A; Fattapposta, F; Pierelli, F; Pozzessere, G; Scoppetta, C; Soldati, G, 1998)	0.3
" Two blood samples were taken from each subject at varying times during the levodopa dosage interval, and the exact time and dosage of levodopa were noted."	( Effect of oral levodopa treatment on articulatory function in Parkinson's disease: preliminary results. Cahill, LM; Charles, BG; Murdoch, BE; Theodoros, DG; Triggs, EJ; Yao, AA, 1998)	0.88
"A neural network model of movement control in normal and Parkinson's disease (PD) conditions is proposed to simulate the time-varying dose-response relationship underlying the effects of levodopa on movement amplitude and movement duration in PD patients."	( Neural dynamics of short and medium-term motor control effects of levodopa therapy in Parkinson's disease. Contreras-Vidal, JL; Poluha, P; Stelmach, GE; Teulings, HL, 1998)	0.73
" Levodopa dose-response curves for antiparkinsonian and dyskinetic effects were then compared for each study arm."	( Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease. Chase, TN; Del Dotto, P; Natté, R; van den Munckhof, P; Verhagen Metman, L, 1998)	1.51
" Since Shy-Drager syndrome is often treated with antiparkinsonian drugs, neuroleptic malignant syndrome can possibly develop after the change in dosage of catecholaminergic drugs."	( [A case of impending neuroleptic malignant syndrome associated with Shy-Drager syndrome]. Egi, N; Harada, T; Kumagai, R; Kurokawa, K; Nakamura, S; Okazaki, M; Shimote, K, 1998)	0.3
" There was no difference in age, duration or stage of PD, or dosage or duration of levodopa therapy between the two groups."	( Poor visual discrimination and visual hallucinations in Parkinson's disease. Diederich, NJ; Goetz, CG; Leurgans, S; Pappert, EJ; Piery, V; Raman, R, )	0.36
" The inhibition of platelet MAO-B activity against multiple dosing of selegiline (2."	( Is 10 milligrams selegiline essential as an adjunct therapy for the symptomatic treatment of Parkinson's disease? Mahmood, I, 1998)	0.3
" The dose-response curve obtained from the denervated striatum showed a shift to the right."	( Loss of regulation by presynaptic dopamine D2 receptors of exogenous L-DOPA-derived dopamine release in the dopaminergic denervated striatum. Kannari, K; Maeda, T; Matsunaga, M; Suda, T, 1999)	0.3
" A short terminal disposition half-life of 2 hours mandates dosing 3 times/day."	( Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Guay, DR, 1999)	0.3
" At the same time, the lower levodopa dosage in the selegiline group was accompanied by at least equal therapeutic efficacy (which is necessary for an unambiguous interpretation)."	( SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Conrad, B; Dichgans, J; Kraus, PH; Krauseneck, P; Pergande, G; Przuntek, H; Rinne, U; Schimrigk, K; Schnitker, J; Vogel, HP, 1999)	0.81
" There was no relationship between TH mRNA expression disease duration or L-dopa dosage in the IPD group."	( The vulnerability of nigral neurons to Parkinson's disease is unrelated to their intrinsic capacity for dopamine synthesis: an in situ hybridization study. Foster, OJ; Kingsbury, AE; Marsden, CD, 1999)	0.3
" Patients with complex fluctuations and diphasic dyskinesias were excluded and the conversion was made after some recommendations, depending on the clinical problems and the daily dosage and administration schedule of standard (STD) Sinemet."	( Controlled release levodopa in Parkinson's disease: influence of selection criteria and conversion recommendations in the clinical outcome of 450 patients. STAR Study Group. Bravo, JL; Grandas, F; Linazasoro, G; Martínez Martín, P, )	0.46
" At doses of 200 mg 2 to 10 times daily coadministered with levodopa/carbidopa or levodopa/benserazide entacapone may increase the duration of clinical response both after the first single dose and after repeated dosing in patients with end-of-dose fluctuations."	( [Entacapone: is it useful as complimentary treatment with levodopa?]. Burguera, JA; Grandas, F; Horga de la Parte, JF; Kulisevsky, J; Luquin, R; Martí, F; Matías-Guiu, J; Obeso, JA, )	0.62
" They both potentiated the effects of L-DOPA in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease, dosed at 10 mg/kg ip, but 48 was not active at 30 mg/kg po."	( Subtype-selective N-methyl-D-aspartate receptor antagonists: synthesis and biological evaluation of 1-(arylalkynyl)-4-benzylpiperidines. Bigge, CF; Boxer, PA; Cai, SX; Gregory, TF; Hawkinson, JE; Konkoy, CS; Meltzer, LT; Serpa, K; Whittemore, ER; Wise, LD; Woodward, RM; Wright, JL; Zhou, ZL, 1999)	0.3
" No patient showed dose-response motor flutuations during levodopa treatment."	( Drug-induced motor complications in dopa-responsive dystonia: implications for the pathogenesis of dyskinesias and motor fluctuations. de la Fuente-Fernández, R, )	0.38
" The present study was conducted in order to evaluate the pharmacokinetics of entacapone after multiple dosing and the pattern of COMT inhibition in erythrocytes during the first day of dosing as well as during steady state."	( Pharmacokinetics of oral entacapone after frequent multiple dosing and effects on levodopa disposition. Gordin, A; Huhtala, S; Huupponen, R; Korpela, K; Reinikainen, K; Rouru, J; Savontaus, E; Scheinin, M, 1999)	0.53
" There were no indications of accumulation of COMT inhibition during frequent dosing of entacapone."	( Pharmacokinetics of oral entacapone after frequent multiple dosing and effects on levodopa disposition. Gordin, A; Huhtala, S; Huupponen, R; Korpela, K; Reinikainen, K; Rouru, J; Savontaus, E; Scheinin, M, 1999)	0.53
"Even when dosed frequently, there are neither indications of accumulation of entacapone nor of its COMT inhibiting activity."	( Pharmacokinetics of oral entacapone after frequent multiple dosing and effects on levodopa disposition. Gordin, A; Huhtala, S; Huupponen, R; Korpela, K; Reinikainen, K; Rouru, J; Savontaus, E; Scheinin, M, 1999)	0.53
" Since the pre- and post-pallidotomy daily levodopa dosage remained essentially the same, the improvement in LID could not be attributed to a reduction in levodopa."	( Levodopa-induced dyskinesias treated by pallidotomy. Ben-Arie, L; Grossman, R; Jankovic, J; Krauss, JK; Lai, E, 1999)	2.01
" Although parkinsonian symptoms responded poorly to levodopa, AEO worsened after increasing levodopa dosage and disappeared when levodopa was discontinued."	( "Apraxia of eyelid opening" induced by levodopa therapy and apomorphine in atypical parkinsonism (possible progressive supranuclear palsy): a case report. De Mari, M; De Salvia, R; Defazio, G; Giorelli, M; Lamberti, P; Livrea, P, )	0.65
" When dosed orally, this compound potentiates the effects of L-DOPA in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease."	( Discovery of subtype-selective NMDA receptor ligands: 4-benzyl-1-piperidinylalkynylpyrroles, pyrazoles and imidazoles as NR1A/2B antagonists. Boxer, PA; Gregory, TF; Meltzer, LT; Serpa, KA; Wise, LD; Wright, JL, 1999)	0.3
"Two studies were undertaken, a single-dose study and a longitudinal dosing study."	( Levodopa-carbidopa and childhood retinal disease. Bremer, DL; Jende, DL; Leguire, LE; McGregor, ML; Nairus, TM; Rogers, GL; Walson, PD, 1998)	1.74
"05) between change in visual acuity in the single-dose study and the longitudinal dosing study."	( Levodopa-carbidopa and childhood retinal disease. Bremer, DL; Jende, DL; Leguire, LE; McGregor, ML; Nairus, TM; Rogers, GL; Walson, PD, 1998)	1.74
" Although certain exceptions apply, dosage adjustments and drug changes should be instituted slowly."	( Maximizing the benefit of pharmacotherapy in Parkinson's disease. Berchou, RC, 2000)	0.31
"Thirteen older amblyopic children were randomly assigned to receive or not receive part-time occlusion (3 h/day) combined with 7 weeks of oral dosing with levodopa-carbidopa (1."	( Occlusion and levodopa-carbidopa treatment for childhood amblyopia. Bremer, DL; Leguire, LE; McGregor, ML; Rogers, GL; Walson, PD, 1998)	0.86
" Selective adenosine A(2A) receptor antagonists, such as KW-6002, may be one means of reducing the dosage of L-DOPA used in treating Parkinson's disease and are potentially a novel approach to treating the illness both as monotherapy and in combination with dopaminergic drugs."	( Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Jackson, MJ; Jenner, P; Kanda, T; Kase, H; Kuwana, Y; Nakamura, J; Pearce, RK; Smith, LA, 2000)	0.31
" Antiparkinsonian medication dosage did not significantly change during the study period."	( [Efficacy and safety of posteroventral pallidotomy for the treatment of advanced Parkinson's disease]. Ferrer, E; Molinuevo, JL; Nobbe, FA; Rumià, J; Tolosa, E; Valldeoriola, F, 2000)	0.31
" Repeated levodopa dosing is necessary to induce dyskinesia, implying the development of sensitization to levodopa."	( Clinical pharmacology of levodopa-induced dyskinesia. Nutt, JG, 2000)	1.01
" Urine recoveries of the three analytes over one 8 h dosing interval showed that the majority of the excreted levodopa and carbidopa was recovered during the first 4 h, and there is proportionally greater excretion of the carbidopa dose than the levodopa dose."	( Bioavailability studies of oral dosage forms containing levodopa and carbidopa using column-switching chromatography followed by electrochemical detection. Sagar, KA; Smyth, MR, 2000)	0.77
" This study was conducted in parallel with a double-blind, placebo-controlled, dose-response study of the safety and efficacy of tolcapone in combination with levodopa/carbidopa therapy."	( Illness impact and adjustment to Parkinson's disease: before and after treatment with tolcapone. Chernik, D; Dorflinger, E; Waters, C; Welsh, MD, 2000)	0.5
" Clinical studies show that they increase the daily ON time by an average 1 to 3 hours, improve the activities of daily living and allow daily levodopa dosage to be decreased."	( Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Kaakkola, S, 2000)	0.51
" Outcome measures were evolution of L-dopa dosage and Unified Parkinson's Disease Rating Scale scores and subscores, and incidence of motor complications."	( Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson's disease. The French Lisuride Study Group. Allain, H; Bentué-Ferrer, D; Destée, A; Le Cavorzin, P; Patay, M; Petit, H; Schück, S, 2000)	0.57
" All were hospitalized initially to determine optimal dosage and to teach them the technique of self-injection."	( [Apomorphine for treatment of "off-periods" in Parkinson's disease]. Kuritzky, A; Melamed, E; Merims, D; Ziv, I; Zoldan, J, 1999)	0.3
" For patients with residual disability, the dosage was escalated during the first 10 weeks."	( Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group. , 2000)	0.66
" However, poorer quality of life associated with inadequate dosage of levodopa may be the price for a low rate of motor complications in patients with Parkinson's disease."	( Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study. Quinn, N; Schrag, A, 2000)	0.54
" The dosing schedule was one tablet TID for 1 week, 1 1/2 tablets TID for 1 week, then two tablets TID for 6 weeks."	( Carbidopa/levodopa for smoking cessation: a pilot study with negative results. Ahlskog, JE; Croghan, GA; Croghan, IT; Hurt, RD; Moyer, TP; Offord, KP; Wolter, TD, 2000)	0.71
" These findings suggest that pramipexole can markedly reduce the daily levodopa dosage without deterioration of motor response and support that this new selective D2/D3 receptor agonist also improves later levodopa-associated motor complications."	( An open-label, multicentre clinical trial to determine the levodopa dose-sparing capacity of pramipexole in patients with idiopathic Parkinson's disease. Hebenstreit, E; Pinter, MM; Rutgers, AW, 2000)	0.78
" This paper reviews the pharmacokinetics, dosing schedule, peripheral and central effects, and safety profile of these agents."	( Issues important for rational COMT inhibition. Dingemanse, J, 2000)	0.31
"In bioequivalence studies, the first blood or plasma sample taken after dosing sometimes yields a higher assayed drug concentration than any samples drawn thereafter."	( First measured plasma concentration value as C(max); impact on the C(max) confidence interval in bioequivalence studies. Conner, D; Jackson, A; Miller, R, 2000)	0.31
" Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors."	( Dyskinesia in Parkinson's disease. Pathophysiology and clinical risk factors. Baas, H, 2000)	0.58
" The study showed that repeated dosing of entacapone inhibits the COMT activity in a dose-dependent manner and thereby reduces the loss of L-Dopa to 3-OMD."	( The effects of different repeated doses of entacapone on the pharmacokinetics of L-Dopa and on the clinical response to L-Dopa in Parkinson's disease. Gordin, A; Heikkinen, H; Koller, WC; LeWitt, PA; Nutt, JG, )	0.13
"To develop stable liquid dosage forms of levodopa-carbidopa for use in children with amblyopia."	( Development of two stable oral suspensions of levodopa-carbidopa for children with amblyopia. Leguire, LE; Morosco, RS; Nahata, MC, )	0.66
" Therapeutic drug monitoring might be useful to explain these modifications in relation to the clinical effect and even to possible problems in transport competition and so to define the LD dosage regimen."	( Monitoring of L-dopa concentrations in Parkinson's disease. Benetello, P; Furlanut , M; Furlanut, M, 2001)	0.31
"To examine the short- and long-duration responses to levodopa dosing in subjects with DRD."	( Response to levodopa treatment in dopa-responsive dystonia. Nutt, JG; Nygaard, TG, 2001)	0.94
"The short-duration response to levodopa dosing seems to develop more slowly and persists longer in subjects with DRD than in subjects with Parkinson disease."	( Response to levodopa treatment in dopa-responsive dystonia. Nutt, JG; Nygaard, TG, 2001)	0.98
" At week 4, 116 eligible patients entered an 8-week double-blind treatment period and were randomized to receive tolcapone three times daily at either 100 mg (group 1; n = 58) or 200 mg (group 2; n = 58) until week 8, followed by the alternative tolcapone dosage until week 12."	( Comparison of two dosages of tolcapone added to levodopa in nonfluctuating patients with PD. Bailey, P; Bulger, L; Facciponte, G; Pourcher, E; Suchowersky, O, )	0.39
" The occurrence of dyskinesia correlated with plasma concentrations of L-dopa, with animals displaying the most severe dyskinesias having significantly higher plasma concentrations of L-dopa one hour after dosing than animals with mild or moderate dyskinesia or no dyskinesia."	( L-dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic observations. Heikkilä, M; Jenner, P; Lindén, IB; Pearce, RK, 2001)	0.31
" In this pilot trial of five patients with tardive and four patients with idiopathic dystonia we tested the effect of morphinsulfate in a retarded form with a dosage of 20-60 mg per day."	( Morphine in tardive and idiopathic dystonia (short communication). Becker, G; Berg, D; Naumann, M; Reiners, K, 2001)	0.31
" From a practical point of view, knowledge of individual patients' kinetic-dynamic variables can help the physician assess patients' clinical needs objectively and optimize levodopa dosing according to disease progression."	( Levodopa therapy monitoring in patients with Parkinson disease: a kinetic-dynamic approach. Albani, F; Avoni, P; Baruzzi, A; Contin, M; Martinelli, P; Riva, R, 2001)	1.95
" Since antiparkinsonian medication has short- and long-term effects that may prevent an estimate of the maximal possible impact of STN DBS, such medication was used at the lowest possible dosage after DBS implantation."	( Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up. Ghika, J; Pollo, C; Pralong, E; Temperli, P; Villemure, JG; Vingerhoets, FJ, 2002)	0.62
" All medications were stopped before implantation and reintroduced, at the lowest dosage needed, only if the postoperative motor score did not reach the baseline level."	( Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up. Ghika, J; Pollo, C; Pralong, E; Temperli, P; Villemure, JG; Vingerhoets, FJ, 2002)	0.62
"We studied the relationship of nonmotor fluctuations with motor symptoms and determined the influence of age at disease onset, duration of disease, dosage and duration of levodopa treatment in the appearance of nonmotor fluctuations."	( The clinical profile of nonmotor fluctuations in Parkinson's disease patients. Aktan, S; Bekiroglu, N; Gunal, DI; Nurichalichi, K; Tuncer, N, 2002)	0.51
" Levodopa and carbidopa combination in 2 different dosage schedules were given to both adults and children."	( Effect of levodopa and carbidopa in human amblyopia. Chaudhuri, Z; Kumar, M; Pandey, PK; Satyabala, K; Sharma, P, )	1.44
" For patients with residual disability, the dosage was escalated during the first 10 weeks, and subsequently, open-label levodopa could be added."	( Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. , 2002)	0.75
"A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry."	( A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa. Brooks, DJ; Brunt, ER; Korczyn, AD; Montastruc, JL; Stocchi, F, 2002)	0.31
" Our findings suggest that lighter patients with Parkinson's disease probably receive a greater cumulative dosage of LD per kilogram of body weight during long-term treatment, because in clinical practice, LD is administered without any adjustment of the dose to body weight."	( Body weight influences pharmacokinetics of levodopa in Parkinson's disease. Arabia, G; Bagalà, A; Bastone, L; Bonavita, S; Caracciolo, M; Crescibene, L; Di Costanzo, A; Gambardella, A; Nicoletti, G; Quattrone, A; Scornaienchi, M; Zappia, M, )	0.39
" In 44 of 58 dosing events, an oral dose of levodopa was related to a peak in plasma concentration."	( Levodopa pharmacokinetics and motor performance during activities of daily living in patients with Parkinson's disease on individual drug combinations. Aquilonius, SM; Gomes-Trolin, C; Lennernäs, H; Nyholm, D, )	1.84
"2 years in the group without falls) and the daily levodopa dosage (on average 806."	( [Analysis of causes for falls in people with Parkinson's disease]. Fiszer, U; Jedynecka, U; Krygowska-Wajs, A; Michałowska, M; Sobieszek, A, )	0.38
" Consumption was expressed in defined daily dosage (DDD) and the costs in euros."	( [The evolution of use of anti-Parkinson drugs in Spain]. Castel, JM; Montané, E; Vallano Ferraz, A, )	0.13
" This entails evaluating the pharmacokinetics and pharmacodynamic actions of the drug regimens used and possibly, dosage form and route of administration of the drugs."	( Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa. Okereke, CS, )	0.33
" Mean dosage of dopaminergic drugs was reduced, but force overflow and dyskinesias were equally improved in 2 patients without a reduction."	( Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus. Deuschl, G; Fietzek, U; Kopper, F; Krack, P; Mehdorn, HM; Müller, D; Poepping, M; Schrader, B; Wenzelburger, R; Zhang, BR, 2002)	0.31
" An analysis of clinical findings showed that: 1) there was a slight amelioration in bradykinesia, rigidity, and smaller dosage of L-DOPA; 2) tremor and drug-induced dyskinesia remained unchanged; 3) subsequently (till 9 years), the clinical effect slightly decreased in almost all patients with PD and in some of them the clinical status became worse than that prior to surgery; 4) repeated NT (2 cases) in the striatum contralaterally did not improved the situation; 5) only neurostimulation of subcortical structures improved clinical results."	( [Neurotransplantation in the treatment of Parkinson disease: follow-up]. Arora, M; Fedorova, NV; Iakovleva, SA; Popov, AP; Shabalov, VA; Shtok, VN; Ugriumov, MV, )	0.13
" Oral administration of high dosage of anticholinergic drugs is firstly recommended for the treatment of dystonia."	( [Medical treatment of dystonia]. Kachi, T, 2001)	0.31
"These findings indicate that subthalamotomy can ameliorate the cardinal symptoms of PD, reduce the dosage of levodopa, diminish complications of the drug therapy, and improve the quality of life."	( Subthalamotomy for advanced Parkinson disease. Liou, HH; Liu, HM; Su, PC; Tseng, HM; Yen, RF, 2002)	0.53
" Serial blood samples were drawn before dosing and up to 24 h after the dose and pharmacokinetic parameters of L-dopa, its metabolites, carbidopa, and entacapone were determined."	( Entacapone improves the availability of L-dopa in plasma by decreasing its peripheral metabolism independent of L-dopa/carbidopa dose. Heikkinen, H; Kaakkola, S; Kela, M; Laine, T; Puttonen, J; Reinikainen, K; Varhe, A, 2002)	0.31
"Thirty (91%) of 33 subjects contacted who participated in three similar 7-week, longitudinal dosing studies returned for follow-up."	( Long-term follow-up of L-dopa treatment in children with amblyopia. Komaromy, KL; Leguire, LE; Nairus, TM; Rogers, GL, )	0.13
" The improvement of peak-dose/diphasic dyskinesias of STN stimulation is considered to be due to the decrease in the daily dosage of antiparkinsonian drugs."	( [Variance in effects of subthalamic nucleus stimulation]. Hamada, I; Hasegawa, N; Okiyama, R; Takahashi, H; Taniguchi, M; Yokochi, F, 2002)	0.31
" The proposed methods were successfully applied to the assay of LD, MD, and DP in various dosage forms."	( Spectrophotometric investigations of the assay of physiologically active catecholamines in pharmaceutical formulations. Keshavayya, J; Melwanki, MB; Nagaralli, BS; Ramesh, KC; Seetharamappa, J, )	0.13
" In this group of patients with most serious motor disability, it has been possible to improve dyskinesia and fluctuations with a relatively important dosage of pergolide and without increase of levodopa dosage."	( [Pergolide: a useful agonist for the treatment of Parkinson disease]. Bonnet, AM; Houeto, JL, 2002)	0.5
" Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors."	( Which factors influence therapeutic decisions in Parkinson's disease? Baas, H; Fuchs, G; Gemende, I; Hueber, R; Lachenmayer, L; Schneider, E; Schoenberger, B; Werner, M, 2002)	0.59
" Our data suggest that during long-term treatment, lighter PD patients, especially women, may receive a greater cumulative dosage of levodopa per kilogram of body weight."	( Body weight, levodopa pharmacokinetics and dyskinesia in Parkinson's disease. Arabia, G; Bagalà, A; Bastone, L; Bosco, D; Caracciolo, M; Crescibene, L; Quattrone, A; Scornaienghi, M; Zappia, M, 2002)	0.89
" In two patients with possible progressive supranuclear palsy, AEO worsened after increasing levodopa dosage or acute apomorphine challenge and disappeared following levodopa discontinuation."	( Frequency of apraxia of eyelid opening in the general population and in patients with extrapyramidal disorders. Aniello, MS; De Mari, M; Defazio, G; Lamberti, P; Zenzola, A, 2002)	0.53
" Statistical differences were observed between UPDRS parts II, III and IV values and daily levodopa dosage in the pre- and postoperative periods, while no differences were evident between the 3 postoperative conditions."	( Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up. Bergamasco, B; Bosticco, E; Lanotte, M; Lopiano, L; Perozzo, P; Rizzone, M; Tavella, A; Torre, E, 2002)	0.54
" This may be achieved by a controlled release (CR) gastroretentive dosage form (GRDF)."	( Novel levodopa gastroretentive dosage form: in-vivo evaluation in dogs. Eyal, S; Friedman, M; Hoffman, A; Klausner, EA; Lavy, E, 2003)	0.8
" Daily dosage of levodopa requirement was reduced by 42%."	( Treatment of advanced Parkinson's disease by subthalamotomy: one-year results. Liou, HH; Liu, HM; Su, PC; Tseng, HM; Yen, RF, 2003)	0.66
" Our data suggest that bcl-2 expression is beneficial only in a limited gene dosage range and that high-level expression of bcl-2 exerts potential deleterious effects."	( Gene dosage-dependent effects of bcl-2 expression on cellular survival and redox status. Evert, BO; Klockgether, T; Schaupp, M; Schulz, JB; Schwarz, CS; Seyfried, J; Wüllner, U, 2003)	0.32
"A new concept for individualising the dosage of drugs in solid form is presented."	( An automatic dose dispenser for microtablets--a new concept for individual dosage of drugs in tablet form. Aquilonius, SM; Bredenberg, S; Nyholm, D; Nyström, C, 2003)	0.32
" Despite the purpose of treatment, the ideal pharmacological drug for PD will include the presence of a safe side-effect profile, a simple dosing schedule, the ability to provide symptomatic relief and the potential to alter disease progression."	( Recent developments in the pharmacological treatment of Parkinson's disease. Riss, J; Tuite, P, 2003)	0.32
" In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites."	( L-DOPA biotransformation: correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. Decker, PA; Dousa, MK; Muenter, MD; Offord, KP; Tyce, GM; Weinshilboum, RM, 2003)	0.32
" This hypothesis is, for many clinicians, the rationale for postponing the employment of and reducing the applied dosage of L-DOPA and for beginning therapy with dopamine receptor agonists or the monoamine oxidase type B (MAO-B) inhibitor selegiline."	( Arguments for the use of dopamine receptor agonists in clinical and preclinical Parkinson's disease. Double, K; Gerlach, M; Reichmann, H; Riederer, P, 2003)	0.32
" In order to simplify the daily dosing of these medications, Orion has developed an entacapone/levodopa/carbidopa combination tablet."	( Entacapone/levodopa/carbidopa combination tablet: Stalevo. , 2003)	0.93
"To design novel expandable gastroretentive dosage form (GRDFs) and evaluate their gastroretentive properties."	( Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on levodopa absorption in humans. Barta, M; Cserepes, E; Friedman, M; Hoffman, A; Klausner, EA; Lavy, E, 2003)	0.54
"1 cm), multi layer dosage forms (DFs) with different rigid polymeric matrices an mechanical properties were folded into gelatin capsules and wer administered to healthy volunteers with a light breakfast."	( Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on levodopa absorption in humans. Barta, M; Cserepes, E; Friedman, M; Hoffman, A; Klausner, EA; Lavy, E, 2003)	0.54
" The off daily duration and the levodopa dosage were significantly reduced in infused patients."	( Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson's disease. Antonini, A; Basile, G; Di Blasi, L; Di Raimondo, G; Di Rosa, AE; Epifanio, A; Imbesi, D; La Spina, P; Martino, G; Morgante, L; Stocchi, F; Tetto, A, 2003)	0.6
" Pronoran ("Servier", France) combined with levodopa was used in dosage 50-150 mg daily during 6 months."	( [Use of pronoran (piribedil) in Parkinson's disease: the results of a multicenter study]. Fedorova, NV, 2003)	0.58
" The mean clozapine dosage was 39."	( Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study. Borg, M; Broussolle, E; Debilly, B; Durif, F; Galitzky, M; Morand, D; Rascol, O; Thobois, S; Viallet, F, 2004)	0.32
" Drug dosage may be reduced by 50%."	( Further experience with extradural motor cortex stimulation for treatment of advanced Parkinson's disease. Report of 3 new cases. Pagni, CA; Zeme, S; Zenga, F, 2003)	0.32
" The galenic form and the dosage of levoDOPA were strictly the same for morning and noon intakes in each patient."	( The effects of a normal protein diet on levodopa plasma kinetics in advanced Parkinson's disease. Bruguerolle, B; Gantcheva, R; Simon, N; Viallet, F, 2004)	0.87
" This problem emerged 2 weeks after the patient's dosage of carbidopa 50 mg-levodopa 200 mg 3 times/day was decreased to twice/day."	( Apraxia of lid opening: dose-dependent response to carbidopa-levodopa. Finley, R; Lee, KC; Miller, B, 2004)	0.79
"The mean (SD) dosage of clozapine was 35."	( Clozapine in drug induced psychosis in Parkinson's disease: a randomised, placebo controlled study with open follow up. Bourdeix, I; Destée, A; Durif, F; Péré, JJ; Pollak, P; Rascol, O; Senard, JM; Tison, F, 2004)	0.32
" Since pramipexole was well tolerated, an ideal dosage to control RLS symptoms could be reached rapidly."	( Low-dose pramipexole in the management of restless legs syndrome. An open label trial. Oertel, WH; Stiasny-Kolster, K, 2004)	0.32
" Long-term use of levodopa is commonly associated with motor complications such as dyskinesia, and both the dosing frequency and total daily dose of levodopa determine the rate of onset and severity."	( Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Jenner, P, 2003)	0.65
" Patients were divided into 3 groups (3, 4 or 5 doses daily) based on their current levodopa dosage frequency."	( Combining entacapone with levodopa/DDCI improves clinical status and quality of life in Parkinson's Disease (PD) patients experiencing wearing-off, regardless of the dosing frequency: results of a large multicentre open-label study. Azulay, JP; Bernhard, G; Giménez-Roldán, S; Markabi, S; Martin, W; Onofrj, M; Schmidt, W; Thomas, A; Vingerhoets, F, 2004)	0.85
" Dosage was escalated during the first 10 weeks for patients with ongoing disability."	( Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Alexander-Brown, B; Atassi, F; Barclay, L; Bennett, S; Berry, D; Biglan, K; Borchert, L; Brocht, A; Brown, D; Daigneault, S; DeAngelis, M; Dillon, S; Dobson, J; Evans, S; Factor, S; Fahn, S; Fontaine, D; Ford, B; Fussell, B; Hall, J; Hammerstad, J; Harrigan, M; Hodgeman, K; Holloway, RG; Hubble, J; Jankovic, J; Kamp, C; Kieburtz, K; Kurlan, R; Lang, A; LeWitt, P; Marek, K; McDermott, M; Miyasaki, J; Montgomery, A; Musch, B; O'Connell, C; Pahwa, R; Panisset, M; Pantella, C; Petsinger, G; Pfeiffer, B; Pfeiffer, R; Rainey, P; Rajput, A; Richard, K; Riley, D; Rodnitzky, R; Ross, T; Rost-Ruffner, E; Russell, DS; Seibyl, J; Shinaman, A; Shirley, T; Shoulson, I; Shults, C; Sime, E; Stacy, M; Standaert, D; Suchowersky, O; Sutherland, L; Tennis, M; Waters, C; Watts, A; Weeks, C; Weiner, W; Welsh, M; Wood, S; Wooten, F, 2004)	0.68
"One could distinguish between "off freezing", which is a symptom tightly bound to L-dopa dosage and titration, and is clinically bound to wearing off, and, on the contrary, "on freezing" which does not respond to therapy modifications or to different drug's titration."	( [Freezing of gait is a symptom of Parkinson disease]. Bandel, D; Capus, L; Mezzarobba, S; Moretti, R; Torre, P, 2004)	0.32
" These data support the notion that pulsatile stimulation contributes to the development of dyskinesia and suggests that more frequent dosing of L-dopa plus entacapone may be a useful treatment strategy for patients in the early stages of Parkinson's disease."	( Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates. Al-Barghouthy, G; Jackson, MJ; Jenner, P; Kuoppamaki, M; Olanow, W; Rose, S; Smith, LA, 2005)	0.64
" Tolcapone produced a greater reduction in levodopa dosage than bromocriptine."	( Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease. Clarke, CE; Deane, KH; Spieker, S, 2004)	0.82
"Twenty-five patients with PD who were taking physician-optimized doses of levodopa/carbidopa (with daytime dosing intervals of 4-8 h) were administered once-daily doses of either donepezil HCl (5 mg) or placebo for 15 days, in two treatment periods, separated by a washout of at least 2 weeks."	( Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. Cullen, EI; Hahne, WA; Kirby, L; Kumar, D; Okereke, CS; Pratt, RD, 2004)	0.81
"Clinical awareness to the structured order of responses and to the effect of dosage can help clinicians in early assessment of response to dopaminergic treatment in VS patients."	( Differential time and related appearance of signs, indicating improvement in the state of consciousness in vegetative state traumatic brain injury (VS-TBI) patients after initiation of dopamine treatment. Groswasser, Z; Keren, O; Krimchansky, BZ; Sazbon, L, 2004)	0.32
", dosage decrement or discontinuation of an antiparkinsonian agent) or had started a benzodiazepine in the 180 days before the start of the antipsychotic or before a randomly chosen index date in the controls."	( Decrease of antiparkinsonian drugs before start of an antipsychotic in patients on levodopa treatment? de Boer, A; Jansen, PA; Porsius, AJ; Roos, RA; van de Vijver, DA, 2004)	0.55
" Previous reports have indicated that ascorbic acid (AsA) can reduce LD dosage without losing its effectiveness."	( The effect of ascorbic acid on the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Hamamoto, M; Katayama, Y; Nagayama, H; Nito, C; Ueda, M; Yamaguchi, H, )	0.38
" There was a good response to levodopa therapy as well as cysticidal therapy with albendazole, allowing later reduction of levodopa dosage in one patient and complete withdrawal in the other."	( Parkinsonism associated with neurocysticercosis. Sá, DS; Teive, HA; Troiano, AR; Werneck, LC, 2005)	0.62
" A poorer response to levodopa was associated with increased mortality independent of disease severity or dosage of levodopa."	( Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort. Lang, AE; Marras, C; McDermott, MP; Naglie, G; Rochon, PA; Rudolph, A; Tanner, CM, 2005)	0.64
" CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation."	( Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats. Akalan, N; Arica, B; Hincal, AA; Kaş, HS; Moghdam, A, 2005)	0.73
"Subjects aged > or =18 years with PD controlled using a stable dosage of C-L were enrolled in this multicenter, open-label, sequential study."	( A multicenter, open-label, sequential study comparing preferences for carbidopa-levodopa orally disintegrating tablets and conventional tablets in subjects with Parkinson's disease. DeRoche, C; Kastenholz, KV; Nausieda, PA; Pfeiffer, RF; Slevin, JT; Tagliati, M, 2005)	0.56
" Wearing-off can be treated by dietary manipulation, shortening the dosing interval, substituting sustained-release levodopa, adding amantadine, or monoamine oxidase type B inhibitors, and other options, including catechol-O-methyltransferase inhibitors and the approved dopamine agonists addressed in another chapter."	( Other pharmacological treatments for motor complications and dyskinesias. Waters, C, 2005)	0.54
" The risk of developing motor fluctuations has been linked to disease severity, dosage of levodopa, and the age of the patient."	( Pathophysiology of motor fluctuations in Parkinson's disease. Widnell, K, 2005)	0.55
"Fluctuations in the symptoms of Parkinson's disease (PD), such as wearing-off and on-off effects, and dyskinesias are related to a variety of factors, including duration and dosage of levodopa, age at onset, stress, sleep, food intake, and other pharmacokinetic and pharmacodynamic mechanisms."	( Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations. Jankovic, J, 2005)	0.52
" L-DOPA was used in the form of the drug madopar in dosage of 25,5 mg/kg of body mass daily."	( [Influence of L-DOPA on rat brain depending on individual behavioral features]. Gershteĭn, LM; Sergutina, AV, 2004)	0.32
" The dosage of ropinirole needed to treat the symptoms of restless legs syndrome appears to be much smaller than what is necessary for Parkinson's disease therapy."	( Ropinirole in the treatment of restless legs syndrome. Kakar, RS; Kushida, CA, 2005)	0.33
" The method was successfully applied to the determination of L-dopa in commercial dosage forms without any pre-treatment."	( A disposable electrochemical sensor for the rapid determination of levodopa. Bergamini, MF; Santos, AL; Stradiotto, NR; Zanoni, MV, 2005)	0.56
" Squirrel monkeys were rendered parkinsonian by chronic administration of MPTP and subsequently dosed with vehicle, L-DOPA plus carbidopa (L-DOPA), ropinirole, or sumanirole over a duration of 8 weeks."	( The effects of a selective dopamine D2 receptor agonist on behavioral and pathological outcome in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys. Childs, MA; Connell, MA; Emborg, ME; Hajos-Korcsok, E; Meglasson, MD; Stephenson, DT, 2005)	0.33
" Levodopa dosage may be reduced by 50%."	( Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and first results by the study group of the Italian neurosurgical society. Altibrandi, MG; Bentivoglio, A; Caruso, G; Cioni, B; Fiorella, C; Insola, A; Lavano, A; Maina, R; Mazzone, P; Pagni, CA; Signorelli, CD; Sturiale, C; Valzania, F; Zeme, S; Zenga, F, 2005)	1.24
" The dosage of L-dopa could be reduced in 31% of the patients."	( [Practical experience on improving activities of daily living competence in Parkinson's patients treated with ropinirole. Results of a applied study]. Angersbach, D; Buchwald, B; Reichmann, H, 2005)	0.33
" There was a trend for lower daily levodopa equivalence dosage and more severe dyskinesia score among females but these differences did not reach statistical significance after Bonferroni correction."	( Gender and the Parkinson's disease phenotype. Baba, Y; Putzke, JD; Uitti, RJ; Whaley, NR; Wszolek, ZK, 2005)	0.61
" Twenty-one treated PD patients received LD/CD and then the identical oral LD dosage of LCE within a standardized setting on 2 consecutive days."	( Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels. Bremen, D; Erdmann, C; Muhlack, S; Müller, T; Przuntek, H; Woitalla, D, 2006)	0.57
" The dosage was gradually escalated over 9 weeks and then maintained until Week 40, at which time active treatment was withdrawn over 3 days."	( Does levodopa slow or hasten the rate of progression of Parkinson's disease? Fahn, S, 2005)	0.84
" OTHER OBSERVATIONS: The ELLDOPA study was the first levodopa dose-response study ever conducted."	( Does levodopa slow or hasten the rate of progression of Parkinson's disease? Fahn, S, 2005)	1.09
"The therapeutic success of L-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease (PD) patients remains controversial as many patients become tolerant requiring higher dosage regimens."	( l-DOPA administration enhances 6-hydroxydopamine generation. Daya, S; Maharaj, H; Mokokong, R; Scheepers, M; Sukhdev Maharaj, D, 2005)	0.33
" The model accounted for levodopa dosing prior to each trial and endogenous levodopa synthesis."	( Importance of within subject variation in levodopa pharmacokinetics: a 4 year cohort study in Parkinson's disease. Chan, PL; Holford, NH; Nutt, JG, 2005)	0.9
" After the first GCRC admission patients were treated with oral levodopa dosed for optimal control of Parkinsonism."	( Pharmacokinetic and pharmacodynamic changes during the first four years of levodopa treatment in Parkinson's disease. Chan, PL; Holford, NH; Nutt, JG, 2005)	0.8
" Animals were assessed for 6 months with the same L-dopa dosing as presurgery as well as chronic oral L-dopa treatment."	( Focal striatal dopamine may potentiate dyskinesias in parkinsonian monkeys. Bankiewicz, KS; Bringas, J; Cunningham, J; Daadi, M; Eberling, JL; Forsayeth, JR; Pivirotto, P; Sanftner, L, 2006)	0.33
" Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia."	( Morphine reward in dopamine-deficient mice. Hnasko, TS; Palmiter, RD; Sotak, BN, 2005)	0.33
"A sensitive, reliable and reproducible HPLC method with electrochemical detection (HPLC-ECD) has been developed for the separation and quantification of levodopa methyl ester (LDME) and its impurities such as levodopa (l-DOPA), 3-methoxytyrosine (MTS) and l-tyrosine (TS) in bulk drug and pharmaceutical dosage form."	( Determination, purity assessment and chiral separation of levodopa methyl ester in bulk and formulation pharmaceuticals. Fang, Y; Wang, J, 2006)	0.78
" Duration of the disease was longer, its stage more advanced, daily levodopa dosage higher, and the proportion of patients with abnormalities in the EEG apparently greater in the group with falls."	( Falls in Parkinson's disease. Causes and impact on patients' quality of life. Fiszer, U; Krygowska-Wajs, A; Michałowska, M; Owczarek, K, )	0.37
" These results suggest that at this dosage and under these specific conditions, timing is dopamine-mediated but the effect of aging on time production is not."	( Single-dose levodopa administration and aging independently disrupt time production. Li, T; Malapani, C; Rakitin, BC; Scarmeas, N; Stern, Y, 2006)	0.71
" LD daily dosage appeared to be inversely correlated with ROS levels and positively associated with GR activity, suggesting a protective role for LD on PBMCs redox status."	( Oxidative stress in peripheral blood mononuclear cells from patients with Parkinson's disease: negative correlation with levodopa dosage. Andreoni, S; Begni, B; Beretta, S; Brighina, L; Ferrarese, C; Galbussera, A; Garofalo, R; Piolti, R; Prigione, A, 2006)	0.54
" However, patients still encounter difficulties in non-specialist settings where there is often confusion over drug selection, dosage and the timing of dosages."	( Identifying poor symptom control in Parkinson's disease. Scott, L, )	0.13
" Not optimum treated hospitalised patients with Parkinson's disease received the same LD dosage on the first day only with carbidopa (CD) and on the second day with CD and EN (t."	( Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease. Bremen, D; Erdmann, C; Goetze, O; Muhlack, S; Müller, T; Przuntek, H; Woitalla, D, 2006)	0.63
" Objectives were to simultaneously determine plasma LD elimination, gastric emptying, and clinical response after a single intake of the same LD dosage as LD/CD--or as (LD/CD/EN) formulation on 2 consecutive days."	( Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Bremen, D; Erdmann, C; Goetze, O; Muhlack, S; Müller, T; Schmidt, WE; Woitalla, D, )	0.42
" Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed."	( Subthalamic deep brain stimulation in patients with a previous pallidotomy. Almaguer, M; Jankovic, J; Ondo, WG; Silay, Y, 2006)	0.54
" Factors associated with levodopa side effects were earlier age of onset, long duration of disease, advanced stage, higher levodopa dosage and long duration of levodopa treatment."	( Levodopa induced motor complications in Thai Parkinson's disease patients. Kulkantrakorn, K; Pongchaiyakul, C; Pulkes, T; Tiamkao, S, 2006)	2.08
" PD medications were unchanged during the study, and levetiracetam was slowly titrated up to a maximum dosage of 3,000 mg/d over a 2-month period."	( Efficacy and tolerability of levetiracetam in Parkinson disease patients with levodopa-induced dyskinesia. Lyons, KE; Pahwa, R, )	0.36
"We examined the direct effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on levodopa-induced peak-dose dyskinesia in 45 patients with Parkinson's disease (PD) without reducing the levodopa dosage during the early period after surgery."	( Direct effect of subthalamic nucleus stimulation on levodopa-induced peak-dose dyskinesia in patients with Parkinson's disease. Fukaya, C; Kano, T; Katayama, Y; Kobayashi, K; Oshima, H; Yamamoto, T, 2006)	0.8
" Dyskinesia is unwanted, sometimes excessive and causes abnormal facial, body and limb movements that appear in many PD patients who are often dependent on the overall dosage of dopaminergic substitution."	( Levodopa, motor fluctuations and dyskinesia in Parkinson's disease. Müller, T; Russ, H, 2006)	1.78
" Daily dosage of levodopa was reduced by 15% at 6 months."	( Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Chung, SJ; Jeon, SR; Kim, SR; Lee, MC; Sung, YH, 2006)	0.67
" Rather, the clinical results indicated that the symptoms had progressed much less than placebo, and in a dose-response manner."	( A new look at levodopa based on the ELLDOPA study. Fahn, S, 2006)	0.69
" Therefore, safinamide may be used in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to test disease-modifying potential."	( Safinamide: from molecular targets to a new anti-Parkinson drug. Caccia, C; Calabresi, M; Curatolo, L; Faravelli, L; Fariello, RG; Maestroni, S; Maj, R; Salvati, P, 2006)	0.33
" The choices available to alleviate these motor fluctuations range from altering the patient's levodopa/carbidopa dosing schedule to the addition of other agents to the regimen, including dopamine receptor agonists, catechol-O-methyltransferase inhibitors, monoamine oxidase inhibitors, and amantadine, as well as implementing dietary changes."	( Motor fluctuations in Parkinson's disease. Weiner, WJ, 2006)	0.55
" Finally, after determination of basal levels of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) in the rats, the rats were dosed with benserazide followed by l-3,4-dihydroxyphenylalanine (l-DOPA)."	( Evaluation of an osmotic pump for microdialysis sampling in an awake and untethered rat. Cooper, JD; Davies, MI; Heppert, KE; Lunte, SM, 2007)	0.34
" Outcome measures included changes in mean medication dosage (levodopa and dopamine agonists), Unified Parkinson's Disease Rating Scale (UPDRS Parts II-III and Item 39), and dyskinesias (Abnormal Involuntary Movements Scale [AIMS])."	( Extradural motor cortex stimulation in Parkinson's disease. Antonini, A; Cilia, R; Landi, A; Pezzoli, G; Sganzerla, E; Vergani, F, 2007)	0.58
" Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h."	( Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms. Amighi, K; Goole, J; Vanderbist, F, 2007)	0.6
"Mood fluctuations related to levodopa (LD) dosing are well-known psychiatric complications of Parkinson's disease (PD)."	( Acute effects of immediate and controlled-release levodopa on mood in Parkinson's disease: A double-blind study. Barbanoj, M; García-Sánchez, C; Gironell, A; Kulisevsky, J; Pagonabarraga, J; Pascual-Sedano, B, 2007)	0.88
" The first change in antiparkinsonian drug treatment, defined as an increase in the daily dosage of any antiparkinsonian drug, the start of a new antiparkinsonian drug or a change in the dosage form during the follow-up period, was taken as an endpoint."	( Influence of initial use of serotonergic antidepressants on antiparkinsonian drug use in levodopa-using patients. Arbouw, ME; Egberts, TC; Guchelaar, HJ; Movig, KL; Neef, C, 2007)	0.56
"To determine if repeated dosing with methylphenidate hydrochloride (MPD) (Ritalin; Novartis Pharmaceuticals, East Hanover, NJ), an inhibitor of the dopamine transporter, would augment the effects of oral levodopa in patients with Parkinson disease."	( Effects of methylphenidate on response to oral levodopa: a double-blind clinical trial. Carlson, NE; Carter, JH; Nutt, JG, 2007)	0.78
" Oral levodopa dosage was decreased as clinically feasible during the first 4 days in the GCRC during open-label administration of MPD and hourly monitoring of parkinsonism and vital signs between 7 am and 8 pm."	( Effects of methylphenidate on response to oral levodopa: a double-blind clinical trial. Carlson, NE; Carter, JH; Nutt, JG, 2007)	1.08
" L-DOPA was administered subchronically for 11 days (beginning 3 days after last MPTP/NaCl injection) or for 14 days (with dosing started immediately following the last MPTP/NaCl injection)."	( The effect of subchronic, intermittent L-DOPA treatment on neuronal nitric oxide synthase and soluble guanylyl cyclase expression and activity in the striatum and midbrain of normal and MPTP-treated mice. Chalimoniuk, M; Langfort, J, 2007)	0.34
" Altering dopaminergic dosing and timing can abate dyskinesias, but usually impact the control of parkinsonism."	( Levodopa-induced dyskinesias. Brotchie, JM; Fabbrini, G; Goetz, CG; Grandas, F; Nomoto, M, 2007)	1.78
" In young parkinsonian patients with mild motor dysfunction, use of levodopa may be delayed or the dosage minimised."	( When should levodopa therapy be initiated in patients with Parkinson's disease? Fernandez, HH; Halkias, IA; Haq, I; Huang, Z, 2007)	0.95
" Sometimes excessive abnormal facial, body and limb movements depend on the overall dosage of dopaminergic substitution."	( [Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy]. Ellrichmann, G; Müller, T; Russ, H, 2007)	0.34
"Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations."	( Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease. Durner, J; Fuchs, G; Greulich, W; Henningsen, H; Herting, B; Jost, WH; Koch, R; Kuhn, W; Kupsch, A; Müller, T; Niklowitz, P; Oertel, WH; Reichmann, H; Spiegel, J; Storch, A; Vieregge, P, 2007)	0.34
" The therapeutic and preventative strategies for LID include using a lower dosage of levodopa, employing dopamine agonists as initial therapy in Parkinson's disease, amantadine, atypical neuroleptics, and neurosurgery."	( Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment. Lo, N; Robinson, T; Thanvi, B, 2007)	2.01
" We compared the motor response after once dosing of 200 mg retarded release LD (levodopa)/CD (carbidopa) and of 150 mg LD/CD/EN (entacapone) by rating of motor symptoms, by measurement of LD- and 3-O-methyldopa (3-OMD) plasma concentrations and by the outcomes of a line tracing task."	( Comparison of 200 mg retarded release levodopa/carbidopa - with 150 mg levodopa/carbidopa/entacapone application: pharmacokinetics and efficacy in patients with Parkinson's disease. Ander, L; Kolf, K; Muhlack, S; Müller, T; Woitalla, D, 2007)	0.84
" Based on the POETRY results, it is hypothesized that estrogen replacement therapy (ERT) may lead to improvement in PD symptoms and provide an opportunity to reduce the dosage of antiparkinsonian medication in women."	( Gender differences in Parkinson's disease. Shulman, LM, 2007)	0.34
" Here, we present a case of PTPS deficiency which showed a more significant correlation of dosage of L-Dopa/carbidopa with serum prolactin levels than with CSF HVA levels."	( A case of 6-pyruvoyl-tetrahydropterin synthase deficiency demonstrates a more significant correlation of L-Dopa dosage with serum prolactin levels than CSF homovanillic acid levels. Kanazawa, M; Kitani, Y; Kohno, Y; Ogawa, A; Shintaku, H; Takayanagi, M, 2008)	0.35
" However, dyskinesia can also consist of dystonia or myoclonus and occur during other parts of the levodopa dosing cycle."	( Levodopa-induced dyskinesia in Parkinson's disease: epidemiology, etiology, and treatment. Hauser, RA; Sullivan, KL; Zesiewicz, TA, 2007)	2
" Thus, rasagiline, administered as a simple and convenient dosage regimen, is a well tolerated and effective option for monotherapy in patients with early Parkinson's disease and for adjunctive therapy in patients with moderate to advanced disease."	( Rasagiline: a review of its use in the management of Parkinson's disease. Keating, GM; Oldfield, V; Perry, CM, 2007)	0.34
" Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis."	( Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5. Baker, M; Burkhard, PR; Cannon, A; Cobb, SA; Coon, KD; Farrer, MJ; Gass, J; Ghika, J; Hauf, M; Hutton, M; Kachergus, JM; Kapatos, G; Melquist, S; Schorderet, DF; Solida, A; Stephan, DA; Vingerhoets, FJ; Wider, C; Wszolek, ZK, 2008)	0.35
" No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1."	( Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5. Baker, M; Burkhard, PR; Cannon, A; Cobb, SA; Coon, KD; Farrer, MJ; Gass, J; Ghika, J; Hauf, M; Hutton, M; Kachergus, JM; Kapatos, G; Melquist, S; Schorderet, DF; Solida, A; Stephan, DA; Vingerhoets, FJ; Wider, C; Wszolek, ZK, 2008)	0.35
" Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis."	( Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5. Baker, M; Burkhard, PR; Cannon, A; Cobb, SA; Coon, KD; Farrer, MJ; Gass, J; Ghika, J; Hauf, M; Hutton, M; Kachergus, JM; Kapatos, G; Melquist, S; Schorderet, DF; Solida, A; Stephan, DA; Vingerhoets, FJ; Wider, C; Wszolek, ZK, 2008)	0.35
" When choosing one of these drugs one should consider its efficacy in monotherapy in early phase and in combined therapy with levodopa in advanced PD, side effects profile, effectiveness in non-motor symptoms of PD, dosing and route of administration."	( [Choosing a dopamine agonist in Parkinson's disease]. Bogucki, A; Gajos, A, )	0.34
" Dyskinesia is usually managed through changes in levodopa dosing or administration; changing the doses of adjunct therapies also may be helpful."	( Optimizing pharmacotherapy: strategies to manage the wearing-off phenomenon. Tse, W, 2006)	0.59
" While it has been suggested that the daily dose of l-DOPA can play a critical role, the mechanisms linking l-DOPA dosage to the occurrence of motor complications have not yet been explored."	( l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation. Angela Cenci, M; Bagetta, V; Barone, I; Bernardi, G; Calabresi, P; Ghiglieri, V; Lindgren, HS; Paillé, V; Picconi, B, 2008)	0.35
" He markedly improved with a very low dosage of L-DOPA/carbidopa, while higher dosages were not tolerated."	( Tyrosine hydroxylase deficiency presenting with a biphasic clinical course. Antonozzi, I; Artiola, C; Carducci, C; Giovanniello, T; Leuzzi, V; Pozzessere, S; Sabato, ML; Santagata, S, 2007)	0.34
" However, due to the short duration of action of conventional levodopa/decarboxylase inhibitor formulations, multiple dosing may be required in individual patients with persisting symptoms."	( Entacapone prolongs the reduction of PLM by levodopa/carbidopa in restless legs syndrome. Ellmén, J; Hirvonen, K; Karvinen, J; Polo, O; Vahteristo, M; Ylä-Sahra, R, )	0.63
"Postoperatively, the mean levodopa dosage was decreased by 27%."	( Effect of bilateral subthalamic nucleus stimulation on levodopa-unresponsive axial symptoms in Parkinson's disease. Goto, S; Hamasaki, T; Kuratsu, JI; Yamada, K, 2008)	0.89
" Thus, a reduction of the total levodopa dosage would be recommended."	( Should levodopa dose be reduced when switched to stalevo? Hernández, B; Kulisevsky, J; Linazasoro, G, 2008)	1.08
" Such 'wearing-off' imposes an escalation in the dosage of the drug, which ultimately fails to provide stable control of motor symptoms and results in the appearance of abnormal involuntary movements or dyskinesia."	( Parkinson's disease: levodopa-induced dyskinesia and signal transduction. Fisone, G; Santini, E; Valjent, E, 2008)	0.66
" Our findings may be explained by differences in the distribution of dopaminergic receptor subtypes in the olfactory system in animals and humans, by relative differences in dosing regimes, or by subtle differences in the respective paradigms."	( Lack of improvement in odor identification by levodopa in humans. Berger, K; Breitenstein, C; Flöel, A; Knecht, S; Rösser, N; Vomhof, P, 2008)	0.6
" In the long-term management of PD, treatment-associated dyskinesia often becomes sufficiently troublesome as to compromise the effective dosing of antiparkinsonian medication."	( Optimizing long-term therapy for Parkinson disease: levodopa, dopamine agonists, and treatment-associated dyskinesia. Galbreath, A; Stacy, M, )	0.38
" All patients received tetrahydrobiopterin replacement in a daily dosage between approximately 2 and 4 mg/kg."	( Long-term follow-up of Taiwanese Chinese patients treated early for 6-pyruvoyl-tetrahydropterin synthase deficiency. Cheng, LY; Hsiao, KJ; Lee, NC; Liu, KM; Liu, TT; Niu, DM, 2008)	0.35
" This report suggests that serum prolactin levels can be a good biomarker for optimal dosage of hydroxylated precursors in long-term treatment monitoring."	( Serum prolactin as a tool for the follow-up of treated DHPR-deficient patients. Concolino, D; Moricca, MT; Muzzi, G; Pascale, MG; Rapsomaniki, M; Strisciuglio, P, 2008)	0.35
"The aim of the present study was to investigate the course of levodopa induced dyskinesia (LID) development in parkinsonian rats treated with several different levodopa dosing regiments."	( The course of dyskinesia induction by different treatment schedules of levodopa in Parkinsonian rats: is continuous dopaminergic stimulation necessary? Evangelou, A; Konitsiotis, S; Marselos, M; Tsironis, C, 2008)	0.82
" Fiber was administered at two different doses, 100 and 400 mg/kg, and the dosage of levodopa/carbidopa was 20:5 mg/kg."	( The hydrosoluble fiber Plantago ovata husk improves levodopa (with carbidopa) bioavailability after repeated administration. Diez, MJ; Fernandez, N; Garcia, JJ; Prieto, C; Sahagun, A; Sierra, M, 2008)	0.82
" The aim of this study was to analyze the presence of DNA damage in peripheral blood lymphocytes (PBL) of PD patients, during a washout and a controlled LD dosage and to evaluate the oxidative damage fluctuation after LD intake."	( Levodopa therapy reduces DNA damage in peripheral blood cells of patients with Parkinson's disease. Aprile, I; Cornetta, T; Cozzi, R; Padua, L; Palma, S; Testa, A; Tonali, P, 2009)	1.8
" Our previous work had shown that intermittent nicotine dosing reduced L-DOPA-induced dyskinetic-like movements in nonhuman primates."	( Continuous and intermittent nicotine treatment reduces L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias in a rat model of Parkinson's disease. Bordia, T; Campos, C; Huang, L; Quik, M, 2008)	0.35
" Given these findings, it is important for physicians to understand the relationship between the pharmacokinetics and pharmacodynamics of levodopa in order to provide dosage regimens that meet patient needs."	( The pharmacokinetics and pharmacodynamics of levodopa in the treatment of Parkinson's disease. Hsu, A; Khor, SP, 2007)	0.8
" The present study was directed toward examining reach-to-eat movements in early PD patients untreated with medication, along with a follow-up examination of a PD patient sub-group who were treated with a symptomatically stable dosage of dopamine replacement."	( Bilateral impairments of skilled reach-to-eat in early Parkinson's disease patients presenting with unilateral or asymmetrical symptoms. Doan, JB; Melvin, KG; Suchowersky, O; Whishaw, IQ, 2008)	0.35
" Medical management includes manipulation of levodopa dosing to establish the optimum treatment schedule, improving levodopa absorption, catechol-O-methyl transferase-inhibition (COMT), Monoamine oxidase-B (MAO-B) inhibition, dopaminergic agonists, amantadine, and continuous dopaminergic infusions."	( Treatment of levodopa-induced motor complications. Olanow, CW; Stocchi, F; Tagliati, M, 2008)	0.97
" Cumulative lifetime L-dopa dosage and fasting MMA levels were associated with PN severity."	( Neuropathy as a potential complication of levodopa use in Parkinson's disease. Brown, MS; Furtado, S; Suchowersky, O; Toth, C; Zochodne, D, 2008)	0.61
" The results of the study revealed that the drug substantially reduced motor deficit, increased the "on"-period, decreased the duration and severity of the "off" period, improved the daily activity and quality of life of patients compared to standard therapy with an additional dosage of levodopa/DDC inhibitor."	( [The clinical-pharmacoeconomic study of efficacy of stalevo in the treatment of Parkinson's disease with motor fluctuations]. Chigir', IP; Dokadina, LV; Fedorova, NV; Levin, OS; Makhnev, SO; Smolentseva, IG, 2008)	0.52
" They underwent an oral levodopa instrumental kinetic-dynamic test on 2 occasions, 4 weeks apart, according to an intrasubject open comparative design: at the first examination, while receiving their usual levodopa/benserazide therapy, and at the second one after a 4-week entacapone (200 mg) dosing concomitantly with usual first morning levodopa/benserazide intake."	( The effect of entacapone on levodopa rate of absorption and latency to motor response in patients with Parkinson disease. Albani, F; Avoni, P; Baruzzi, A; Contin, M; Martinelli, P; Riva, R; Scaglione, C, )	0.73
" Six patients (3F, mean age 62 years) with mild-moderate PD (mean disease duration 6 years, UPDRS-off 13, UPDRS-on 3, H&Y stage 2, daily levodopa dosage 450 mg) were studied off and on levodopa on separate days."	( Spike-timing-related plasticity is preserved in Parkinson's disease and is enhanced by dopamine: evidence from transcranial magnetic stimulation. Mastaglia, FL; Rodrigues, JP; Stell, R; Thickbroom, GW; Walters, SE, 2008)	0.55
" However, the mean pergolide dosage in our study was lower than in previous studies."	( Valvular heart disease in patients with Parkinson's disease treated with pergolide, levodopa or both. Aydemir, T; Bader, H; Cetin, S; Kizkin, S; Meral, H; Ozben, B; Ozben, S; Ozer, F; Ozturk, O; Tiras, R, 2009)	0.58
" Compared to the rest of our PD patients submitted to STN-DBS, the dyskinesia group needed a lower levodopa-equivalent daily dosage (LEDD) over the time of follow-up."	( Transient disabling dyskinesias: a predictor of good outcome in subthalamic nucleus deep brain stimulation in Parkinson's disease. Ayres-Basto, M; Gago, MF; Linhares, P; Rosas, MJ; Sousa, G; Vaz, R, 2009)	0.57
" Accordingly, the dose-response curve for the response to LY379268 in both knockout mice was shifted leftward."	( Enhanced sensitivity to group II mGlu receptor activation at corticostriatal synapses in mice lacking the familial parkinsonism-linked genes PINK1 or Parkin. Bonsi, P; Cuomo, D; Kitada, T; Martella, G; Pisani, A; Platania, P; Sciamanna, G; Shen, J; Tassone, A; Tscherter, A; Vita, D, 2009)	0.35
" A number of therapeutic options are available to optimize therapeutic outcome, including modification of the levodopa dose or dosing schedule,switching to another levodopa formulation and the use of adjunct therapies, such as catechol-O-methyl transferase inhibitors, dopamine agonists and monoamine oxidase-B inhibitors."	( Levodopa-related wearing-off in Parkinson's disease: identification and management. Lyons, KE; Pahwa, R, 2009)	2.01
"Open-label, randomized, two-period, active-controlled, cross-over study with four dosing regimens: groups I and II (healthy volunteers and Parkinson's disease patients) received levodopa 100 mg or 150 mg four times daily, respectively, and groups III and IV (healthy volunteers) received the same strengths of levodopa five times daily."	( Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily. Ellmén, J; Hänninen, J; Hartikainen, P; Kaakkola, S; Kaasinen, V; Kailajärvi, M; Korpela, K; Kuoppamäki, M; Löyttyniemi, E; Lyytinen, J; Marttila, R; Ruokoniemi, P, 2009)	0.81
"The present results on the differences in levodopa PK between LCE and LC provide a basis to evaluate the relationship of levodopa PK and the induction of motor complications in an on-going study in early Parkinson's disease using similar dosing regimens."	( Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily. Ellmén, J; Hänninen, J; Hartikainen, P; Kaakkola, S; Kaasinen, V; Kailajärvi, M; Korpela, K; Kuoppamäki, M; Löyttyniemi, E; Lyytinen, J; Marttila, R; Ruokoniemi, P, 2009)	0.88
" All patients had bilateral symptoms and their levodopa equivalent dosing were analysed."	( Comparison of unilateral pallidotomy and subthalamotomy findings in advanced idiopathic Parkinson's disease. Barlas, O; Coban, A; Hanagasi, HA; Karamursel, S, 2009)	0.61
" The cysteine increase may be due to the significant higher dosing of daily LD/DCI and the significant higher morning LD/DCI dose 1 hour before blood sampling in PD patients with tHcy above 15 when compared with the remaining PD patients and the controls."	( Cysteine elevation in levodopa-treated patients with Parkinson's disease. Kuhn, W; Müller, T, 2009)	0.67
" Daily levodopa dosage per kg and total dopaminergic dosage per kg body weight were negatively correlated with BMI."	( Dopaminergic treatment is associated with decreased body weight in patients with Parkinson's disease and dyskinesias. Bachmann, CG; Brunner, E; Trenkwalder, C; Zapf, A, 2009)	0.81
" Our findings indicate that patients with a lower BMI received a higher cumulative levodopa dosage and that levodopa may be responsible for weight loss in PD."	( Dopaminergic treatment is associated with decreased body weight in patients with Parkinson's disease and dyskinesias. Bachmann, CG; Brunner, E; Trenkwalder, C; Zapf, A, 2009)	0.58
" Also, alpha-syn gene dosage can cause familial PD and inhibition of its gene expression by blocking translation via a newly identified Iron Responsive Element-like RNA sequence in its 5'-untranslated region may provide a new PD drug target."	( Physiological and pathological role of alpha-synuclein in Parkinson's disease through iron mediated oxidative stress; the role of a putative iron-responsive element. Branden, L; Greig, NH; Huang, X; Olivares, D; Rogers, JT, 2009)	0.35
" Patients taking higher dosage of levodopa had fewer NMOS."	( Non-motor off symptoms in Parkinson's disease. Cheon, SM; Kim, JW; Kim, WJ; Park, MJ, 2009)	0.63
"A simple, precise, and accurate high-performance liquid chromatographic method was developed and validated to determine percent drug release of levodopa (LEV), carbidopa (CAR), and entacapone (ENT) from its combination dosage form."	( Development and application of a high-performance liquid chromatographic method for the determination of in vitro drug release of levodopa, carbidopa, and entacapone from a tablet formulation. Doshi, AS; Mehta, TN; Nanda, N; Upadhyay, KJ, )	0.54
" ICD behaviors were associated with an increased mean levodopa equivalent daily dosage and alcohol use (p=0."	( Impulse control disorders in Parkinson's disease in a Chinese population. Chan, P; Ding, H; Fan, W; Ma, J, 2009)	0.6
" In a dose-response study, we identified a dose window leading to >60% decrease in TH(+) neurons without any change in vesicular monoamine transporter-2 (VMAT2) expression."	( Dose optimization for long-term rAAV-mediated RNA interference in the nigrostriatal projection neurons. Aebischer, P; Björklund, T; Kirik, D; Sahin, G; Ulusoy, A, 2009)	0.35
" In this group, substitution with IPX054 reduced dosing frequency while maintaining CD/LD efficacy."	( Reducing dosing frequency of carbidopa/levodopa: double-blind crossover study comparing twice-daily bilayer formulation of carbidopa/levodopa (IPX054) versus 4 daily doses of standard carbidopa/levodopa in stable Parkinson disease patients. Fan, W; Goetz, CG; Hinson, VK; Hsu, A; Leurgans, S; Nguyen, T, )	0.4
"009) and daily levodopa dosage (R(p)=-0."	( Serum uric acid levels in patients with Parkinson's disease: their relationship to treatment and disease duration. Andreadou, E; Boufidou, F; Gournaras, F; Nikolaou, C; Rentzos, M; Tsoutsou, A; Vassilopoulos, D; Zissimopoulos, V; Zournas, C, 2009)	0.71
" The daily administrations of l-dopa were curtailed from 3 or 4 to 2, and the l-dopa dosage was reduced up to 40%."	( Dopamine agonists in 6-pyruvoyl tetrahydropterin synthase deficiency. Concolino, D; Mussa, A; Ponzone, A; Porta, F; Spada, M, 2009)	0.35
" Following oral or intravenous administration of L-dopa plus C-dopa and intranasal dosing of L-dopa in the presence and absence of C-dopa to the rat, the concentrations of L-dopa in plasma and brain were determined using HPLC."	( Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems. Chun, IK; Gwak, HS; Kang, W; Kim, TK; Lee, YH; Oh, SY, 2009)	0.6
" In animals previously exposed to L: -dopa to induce dyskinesia, escalating and repeated dosing of aplindore (0."	( The dopamine D(2) receptor partial agonist aplindore improves motor deficits in MPTP-treated common marmosets alone and combined with L-dopa. Andree, TH; Hansard, M; Hoffman, DC; Hurtt, MR; Jackson, MJ; Jenner, P; Kehne, JH; Pitler, TA; Smith, LA; Stack, G, 2010)	0.36
" For the groups C, D, E and F, the dosage of levodopa administered was also recorded."	( [A multi-centered randomized double-blinded controlled clinical study on efficacy of gulling pa'an capsule in treating Parkinson's disease]. Meng, QG; Yu, XD; Zhao, GH, 2009)	0.61
" GPC shows obvious effects in improving patients' motor syndrome and the quality of life; as used in combining with levodopa, the dosage of levodopa required could be reduced."	( [A multi-centered randomized double-blinded controlled clinical study on efficacy of gulling pa'an capsule in treating Parkinson's disease]. Meng, QG; Yu, XD; Zhao, GH, 2009)	0.56
"8% at 24 weeks best discriminated treatment with levodopa 300 mg/day (a common initial maintenance dosage in clinical practice) from placebo."	( Levodopa response in early Parkinson's disease. Auinger, P; Hauser, RA; Oakes, D, 2009)	2.05
"In this open-label naturalistic study, 75 PD patients (group A) completely switched standard LD (Sinemet or Madopar) with Sirio at an equivalent dosage (800-1000 mg/d)."	( Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study. Antonini, A; Guidi, M; Mancini, F; Martignoni, E; Pacchetti, C; Sciarretta, M; Stocchi, F; Zangaglia, R, )	0.43
" Oral levodopa dosing was increased in 28% of patients; the primary outcome remained significant when these patients were excluded."	( Direct switch from levodopa/benserazide or levodopa/carbidopa to levodopa/carbidopa/entacapone in Parkinson's disease patients with wearing-off: efficacy, safety and feasibility--an open-label, 6-week study. Amar, K; Eggert, K; Kuoppamäki, M; Leinonen, M; Luotonen, L; Nissinen, H; Oertel, W; Skogar, O, 2010)	1.17
"The characteristics of levodopa dosing are not well described in the literature."	( Large differences in levodopa dose requirement in Parkinson's disease: men use higher doses than women. Askmark, H; Karlsson, E; Lundberg, M; Nyholm, D, 2010)	0.99
" Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not."	( Large differences in levodopa dose requirement in Parkinson's disease: men use higher doses than women. Askmark, H; Karlsson, E; Lundberg, M; Nyholm, D, 2010)	0.68
" Then, a dose-response of MPEP and MTEP (1."	( Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. Di Paolo, T; Gasparini, F; Gomez-Mancilla, B; Grégoire, L; Morin, N, 2010)	0.36
" The Cochrane Collaboration guidelines were followed and the following data were extracted from each study: identifier (title and bibliographical reference), classification of the quality of the evidence (Jadad criteria), type and design of the study, number of patients, patient demographics (average age, sex), Parkinson's disease stage (Hoehn and Yahr Scale), treatment (monotherapy or adjuvant to levodopa), drugs used (including dosage and duration), study objective (safety or tolerability), method of evaluation of results, randomization and blinding, and description of all the adverse events in all treatment groups."	( Tolerability and safety of ropinirole versus other dopamine agonists and levodopa in the treatment of Parkinson's disease: meta-analysis of randomized controlled trials. Kulisevsky, J; Pagonabarraga, J, 2010)	0.76
"Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration."	( [Homocysteine and cognitive impairment in Parkinson's disease]. Avilés, F; Cañizares, F; Carles-Díes, R; Fernández-Barreiro, A; Herrero, MT; Martín-Fernández, JJ; Morsi-Hassan, O; Parra, S; Villegas, I, )	0.38
" However, age, PD severity, disease duration and levodopa dosage were similar."	( Long term follow-up of Parkinson's disease patients with impulse control disorders. Demiray, DY; Erginöz, E; Kenangil, G; Ozekmekçi, S; Sohtaoğlu, M, 2010)	0.62
"Although we studied a small number of patients the recovery from compulsive behaviors may be associated with the decrease in DA dosage and increase in levodopa."	( Long term follow-up of Parkinson's disease patients with impulse control disorders. Demiray, DY; Erginöz, E; Kenangil, G; Ozekmekçi, S; Sohtaoğlu, M, 2010)	0.56
" We now report on the choice of dopa decarboxylase inhibitors, dose and the time of dosing relationships of carbidopa, benserazide and L-alpha-methyl dopa (L-AMD) in potentiating the effects of L-DOPA in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated common marmoset."	( The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP-treated common marmoset. Fisher, R; Jackson, MJ; Jenner, P; Rose, S; Tayarani-Binazir, KA; Zoubiane, G, 2010)	0.36
" STN-DBS induced attenuation of her cardinal PD symptoms and marked improvement of dyskinesia without reduction of LD dosage perioperatively."	( Direct relief of levodopa-induced dyskinesia by stimulation in the area above the subthalamic nucleus in a patient with Parkinson's disease--case report. Fukaya, C; Katayama, Y; Kobayashi, K; Nishikawa, Y; Ogasawara, K; Ogawa, A; Oshima, H; Yamamoto, T, 2010)	0.7
"Dissolution studies cannot distinguish phenomena occurring inside the dosage forms when studying formulation with similar dissolution profiles-such formulations can behave differently when considering their physical changes."	( Novel application of MRI technique combined with flow-through cell dissolution apparatus as supportive discriminatory test for evaluation of controlled release formulations. Dorozyński, PP; Jachowicz, R; Kulinowski, P; Mendyk, A; Młynarczyk, A, 2010)	0.36
" This paper reviews the various therapeutic options available for childhood-onset dystonia, with a specific attention to dosage and side effects of the drugs regarding pediatric population according to the data of the literature."	( [Treatment of childhood dystonia]. Bahi-Buisson, N; Doummar, D; Echenne, B; Payet, C; Roubertie, A; Roze, E, 2010)	0.36
" The amount of NT-modified aSN within PBMCs was positively correlated with intracellular ROS concentration and inversely related to daily dosage of levodopa, making its measurement potentially relevant for disease-intervention studies."	( Alpha-synuclein nitration and autophagy response are induced in peripheral blood cells from patients with Parkinson disease. Andreoni, S; Begni, B; Brighina, L; Difrancesco, JC; Ferrarese, C; Galbussera, A; Piazza, F; Piolti, R; Prigione, A, 2010)	0.56
" The preliminary diagnosis was parkinsonism associated with V-P shunting: therefore, the levodopa dosage was increased from 200 mg/day to 600 mg/day."	( [Rapidly progressive parkinsonism that developed one year after ventriculoperitoneal shunting for idiopathic aqueductal stenosis: a case report]. Hayashi, Y; Hozumi, I; Inuzuka, T; Kimura, A; Sakurai, T; Tanaka, Y; Yamada, M, 2010)	0.58
" While levodopa dosage had no relationship to anxiety, experience of dyskinesias or on/off fluctuations increased the risk."	( Anxiety disorders in Parkinson's disease: prevalence and risk factors. Byrne, GJ; Dissanayaka, NN; Marsh, R; Matheson, S; Mellick, GD; O'Sullivan, JD; Sellbach, A; Silburn, PA, 2010)	0.82
" Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most."	( Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke--a randomized, double-blind, placebo-controlled trial. Delbari, A; Lokk, J; Salman Roghani, R, 2011)	0.65
" Our results indicate that effective dosing with A(2A)R antagonists should be tested as monotherapy in early PD, and serves to remind us that positive behavioral effects of such treatment need not be reflected in rescue of striatal dopamine levels."	( Chronic A2A antagonist treatment alleviates parkinsonian locomotor deficiency in MitoPark mice. Fuxe, K; Galter, D; Lindqvist, E; Marcellino, D; Müller, CE; Olson, L; Schneider, M, 2010)	0.36
" As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition."	( Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity. Grundey, J; Liebetanz, D; Monte-Silva, K; Nitsche, MA; Paulus, W, 2010)	0.36
"5%) or dispensation of the wrong carbidopa/levodopa dosage (2/8; 25%)."	( Carbidopa/levodopa pharmacy errors in Parkinson's disease. Khadem, NR; Nirenberg, MJ, 2010)	1.03
" We retrospectively analyzed data from 17 stable HP rhesus monkeys treated long-term with chronic intermittent dosing of levodopa (LD) in an attempt to induce choreoathetoid and dystonic dyskinesias."	( Dyskinesias do not develop after chronic intermittent levodopa therapy in clinically hemiparkinsonian rhesus monkeys. Bakay, RA; Deogaonkar, M; Lieu, CA; Subramanian, T, 2011)	0.83
" The main strategies to assure reproducibility of both intestinal absorption and delivery to the brain, and the clinical effect include standardization of levodopa dosing with respect to meal times and a controlled dietary protein intake."	( Pharmacokinetics of levodopa. Contin, M; Martinelli, P, 2010)	0.88
" The novel integrated approach included measurements of: solvent uptake, erosion, apparent density and changes in the internal structure of dosage forms during dissolution test by means of a USP4 compatible MRI."	( Gastroretentive drug delivery systems with L-dopa based on carrageenans and hydroxypropylmethylcellulose. Dorożyński, P; Jachowicz, R; Kulinowski, P; Mendyk, A, 2011)	0.37
" This is delayed by lower dosage at early stages, made possible by additional treatment with histamine antagonists."	( L-Dopa activates histaminergic neurons. Blandina, P; Haas, HL; Klyuch, BP; Li, S; Lin, JS; Passani, MB; Sergeeva, OA; Yanovsky, Y; Yao, Q, 2011)	0.37
" Therefore, when generating mouse models of LID, strain must be taken into consideration when choosing the L-DOPA dosing regimen."	( Generation of a model of L-DOPA-induced dyskinesia in two different mouse strains. Brotchie, JM; Fahana, N; Johnston, TH; Khademullah, CS; Lam, D; Lo, C; Nash, JE; Talwar, S; Thiele, SL; Warre, R, 2011)	0.37
" For patients preferring mobility over dyskinesia, levodopa should be dosed sufficiently, and possibly titrated, to maximize clinical benefit and patient satisfaction."	( [Patients' perspective on Parkinson disease therapies: results of a large-scale survey in Japan]. Fujimoto, K; Hattori, N; Kondo, T; Murata, M, 2011)	0.62
" Neither disease severity nor L-dopa dosage correlated with plasma AVP levels."	( Increased plasma arginine vasopressin levels in dopamine agonist-treated Parkinson's disease patients. Arai, M, 2011)	0.37
" Despite dosing differences, the PR titration regimen was generally well tolerated, with an AE profile similar to that of IR."	( PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease. Giorgi, L; Hunter, B; Schapira, AH; Stocchi, F, 2011)	0.37
" A nonlinear, inverted U-shaped dose-response curve of its effects on cognition has been observed in animal studies."	( Dose-dependent nonlinear effect of L-DOPA on paired associative stimulation-induced neuroplasticity in humans. Grundey, J; Nitsche, MA; Paulus, W; Thirugnanasambandam, N, 2011)	0.37
" Levodopa CR dosage was adjusted to match the optimal L/DDC dose for each participant."	( A single-blind cross over study investigating the efficacy of standard and controlled release levodopa in combination with entacapone in the treatment of end-of-dose effect in people with Parkinson's disease. Danoudis, M; Iansek, R, 2011)	1.5
"Patients with Parkinson's disease can benefit from controlled released levodopa dosage forms since there is a clear clinical advantage in obtaining sustained plasma concentrations."	( In-vivo evaluation of prolonged release bilayer tablets of anti-Parkinson drugs in Göttingen minipigs. Bonifácio, MJ; Falcão, A; Lobo, JS; Machado, R; Soares-da-Silva, P; Sousa e Silva, JP, 2011)	0.6
" This study demonstrates that gastric-retentive ER dosage forms may reduce dose frequency while minimizing the plasma peak-to-trough fluctuation and consequently reduce motor fluctuation in patients with Parkinson's disease."	( Pharmacokinetics of levodopa/carbidopa delivered from gastric-retentive extended-release formulations in patients with Parkinson's disease. Chen, C; Cowles, VE; Illarioshkin, SN; Stolyarov, ID; Sweeney, M, 2012)	0.7
" Future studies are needed which determine the optimal therapeutic window for and dosage of psychostimulants as well as identify those stroke patients who might benefit the most from treatment."	( Effect of methylphenidate and/or levodopa combined with physiotherapy on mood and cognition after stroke: a randomized, double-blind, placebo-controlled trial. Delbari, A; Lokk, J; Salman-Roghani, R, 2011)	0.65
" At the end of the study, daily medication dosage was reduced in treated patients, whereas it was significantly increased in control patients."	( Effectiveness of intensive inpatient rehabilitation treatment on disease progression in parkinsonian patients: a randomized controlled trial with 1-year follow-up. Balbi, P; Bertotti, G; Boveri, N; Comi, C; Frazzitta, G; Guaglio, G; Maestri, R; Perini, M; Riboldazzi, G; Turla, M; Uccellini, D, 2012)	0.38
"Repeated dosing of levodopa/carbidopa/entacapone (LCE) has shown a favourable pharmacokinetic (PK) profile compared with levodopa/carbidopa (LC), but increases maximum plasma levodopa concentrations (C(max)) during the day."	( The effect of different dosing regimens of levodopa/carbidopa/entacapone on plasma levodopa concentrations. Ellmén, J; Ingman, K; Korpela, I; Kuoppamäki, M; Naukkarinen, T; Vahteristo, M, 2012)	0.97
"5/200 mg (LCE 100 and LCE 150), respectively, would avoid the increase in levodopa C(max) values observed during multiple dosing of LCE 100 and LCE 150."	( The effect of different dosing regimens of levodopa/carbidopa/entacapone on plasma levodopa concentrations. Ellmén, J; Ingman, K; Korpela, I; Kuoppamäki, M; Naukkarinen, T; Vahteristo, M, 2012)	0.87
"2) on stable levodopa dosage were studied."	( Effect of a single dose of standard levodopa on cardiac autonomic function in Parkinson's disease. Datta, K; Ganesan, M; Pal, PK; Sathyaprabha, TN; Sriranjini, SJ, )	0.78
" Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods."	( Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease. Aquilonius, SM; Askmark, H; Hellquist, E; Johansson, A; Lennernäs, H; Nyholm, D, )	1.28
" This case report serves as a reminder of the importance that patients receive their anti-Parkinsonian medications perioperatively, and highlights the potential benefits of inserting a gastric tube to continue anti-Parkinson's medication dosing during prolonged surgery."	( Nasogastric medication for perioperative Parkinson's rigidity during anaesthesia emergence. Grice, T; Stagg, P, 2011)	0.37
" Higher plasma concentrations of levodopa during the first 2 h after dosing were followed by lower plasma concentrations during the third and fourth hours."	( Plasma dopa concentrations after different preparations of levodopa in normal subjects. Groves, MJ; Morris, JG; Parsons, RL; Trounce, JR, 1976)	0.78
"Adherence to regular PD medication dosing schedules during hospitalization is problematic, but improves with specialist consultation."	( Assessment of appropriate medication administration for hospitalized patients with Parkinson's disease. Atassi, F; Fincher, L; Hou, JG; Lai, EC; Moore, S; Nelson, N; Sarwar, A; Ward, C; Wu, LJ; York, M, 2012)	0.38
" Consequently, different L-dopa-sparing strategies have been successively introduced, with partial reduction of L-dopa dosage and amelioration of the clinical outcome."	( Dopamine agonists in dihydropteridine reductase deficiency. Concolino, D; Mussa, A; Ponzone, A; Porta, F; Spada, M, 2012)	0.38
" Dosage of the drug was stable over time."	( Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease. Johansson, A; Klangemo, K; Nyholm, D, 2012)	1.82
"Subjects received CD-LD 3 or 4 times daily for 2 weeks, followed by XP21279 plus CD 3 times daily for 2 weeks at fixed dosing times, allowing dose adjustment to optimize clinical response, in this multiple-dose, multicenter, open-label, 2-period, sequential-treatment study."	( Actively transported levodopa prodrug XP21279: a study in patients with Parkinson disease who experience motor fluctuations. Chen, D; Ellenbogen, A; Huff, FJ; Lal, R; Lewitt, PA; Luo, W; McGuire, K; Zomorodi, K, )	0.45
" However, at the higher dosage of 2 mg/day, rasagiline met the primary endpoint in the TEMPO study and the first, but not the second, of three hierarchical primary endpoints in the ADAGIO study."	( Rasagiline: a review of its use in the treatment of idiopathic Parkinson's disease. Hoy, SM; Keating, GM, 2012)	0.38
"Aiming to explore pharmacological modulation on human motor cortex plasticity, we tested healthy subjects after each dosage of diazepam, levodopa i placebo administration, using paired associative stimulation protocol (PAS) that induce fenomena similar to a long-term potentiation and depression, as defined on the synaptic level."	( [Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: a TMS study]. Grajić, M; Ilić, NV; Ilić, TV; Petrović, I, )	0.64
" Although mean plasma AVP levels are significantly higher in treated PD patients than in treatment-naïve patients, neither disease severity nor levodopa/carbidopa dosage (range, 300/30-850/85 mg) correlates with plasma AVP levels."	( Levodopa in combination with carbidopa does not affect plasma arginine vasopressin levels in treatment-naïve older patients with Parkinson's disease: A before-after study. Arai, M, 2012)	2.02
" The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration."	( Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Aquilonius, SM; Bäckström, T; Ehrnebo, M; Gomes-Trolin, C; Lewander, T; Nyholm, D; Nyström, C; Panagiotidis, G, )	0.7
" Acute dosing led to a worsening of long-term depression in all the groups."	( Acute dopamine boost has a negative effect on plasticity of the primary motor cortex in advanced Parkinson's disease. Balachandran, A; Joseph, T; Kishore, A; Meunier, S; Popa, T; Velayudhan, B, 2012)	0.38
" Few changes in medication treatment patterns were noted following the initial LID, with only slight increases in levodopa dosage and few additions of alternative agents."	( Treatment patterns and associated costs with Parkinson's disease levodopa induced dyskinesia. Mallya, U; Pahwa, R; Suh, DC, 2012)	0.83
" We examined correlates of individual differences in alertness, including demographics, clinical features, nocturnal sleep variables, and class and dosage of anti-Parkinson's medications."	( Daytime alertness in Parkinson's disease: potentially dose-dependent, divergent effects by drug class. Bliwise, DL; Factor, SA; Freeman, A; Greer, SA; Juncos, JJ; Rye, DB; Trotti, LM; Wilson, AG; Wood-Siverio, C, 2012)	0.38
" Pharmacologic options to treat wearing off include adding (or increasing the dosage of) levodopa, adding (or increasing the dosage of) a dopamine agonist, or adjunctive treatment with a monoamine oxidase inhibitor or catechol-O-methyltransferase inhibitor."	( Off spells and dyskinesias: pharmacologic management of motor complications. Khan, TS, 2012)	0.6
"Repeated dosing (2."	( Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers. Aquilonius, SM; Bäckström, T; Ehrnebo, M; Lewander, T; Nyholm, D; Nyström, C; Panagiotidis, G; Spira, J; Trolin, CG, 2013)	0.69
" Daily levodopa dosage was significantly lower at both 6 and 12 months postoperatively."	( Effect of bilateral deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease. Huang, G; Ji, LY; Ji, XT; Li, JM; Liu, WP; Ma, LT; Niu, L; Qu, Y; Zhao, DS, 2012)	0.81
" The significant reduction in levodopa dosage and improvement in neuropsychological function may be the reason for the therapeutic effect seen with STN-DBS."	( Effect of bilateral deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease. Huang, G; Ji, LY; Ji, XT; Li, JM; Liu, WP; Ma, LT; Niu, L; Qu, Y; Zhao, DS, 2012)	0.67
" The relationship between released transmitters and potassium concentration was found to fit to a sigmoidal dose-response curve."	( All polymer chip for amperometric studies of transmitter release from large groups of neuronal cells. Larsen, ST; Taboryski, R, 2012)	0.38
" After their dopaminergic treatment had been changed to a less pulsatile form of administration (ie, the use of dopamine agonist alone in the first patient and an increase in the dosage of dopamine agonist with a low dose of levodopa in the second), these abnormal movements totally disappeared in the first patient and were greatly improved in the second."	( Continuous buccolingual masticatory dyskinesia in Parkinson's disease. Damier, P; Derkinderen, P; Giumelli, B; Meyniel, C, 2012)	0.56
" The dopamine precursor levodopa led to a dose-dependent (inverted U-shape) persistent episodic memory benefit for images of scenes when tested after 6 h, independent of whether encoding-related hippocampal fMRI activity was weak or strong (U-shaped dose-response relationship)."	( Dopamine modulates episodic memory persistence in old age. Bunzeck, N; Chowdhury, R; Dolan, RJ; Düzel, E; Guitart-Masip, M, 2012)	0.69
" We propose an alternative apomorphine challenge test, with a single injection and a higher initial dosage of 2-4 mg, as well as to schedule treatment according to the obtained response at that dosage."	( [Proposed alternative to standard apomorphine challenge test]. Burguera, JA; Martínez-Castrillo, JC, 2012)	0.38
" The type of antipsychotic and the changes in levodopa dosage were determined."	( Management of neuropsychiatric symptoms in long-term care residents with Parkinson's disease: a retrospective cohort study. Anderson, GM; Fischer, HD; Herrmann, N; Marras, C; Rochon, PA; Wang, X, 2013)	0.65
" The first levodopa dosage change was a dose reduction in 469 (98 %) patients, and a dose increase in ten (2 %) patients."	( Management of neuropsychiatric symptoms in long-term care residents with Parkinson's disease: a retrospective cohort study. Anderson, GM; Fischer, HD; Herrmann, N; Marras, C; Rochon, PA; Wang, X, 2013)	0.78
"For best symptom management, careful consideration should be given to scheduling surgery at the earliest possible time, administering medications as close to the patient's usual dosing schedule as possible, and providing nursing education about optimal medication management for this patient population."	( Perioperative medication withholding in patients with Parkinson's disease: a retrospective electronic health records review. Anderson, LC; Fagerlund, K; Gurvich, O, 2013)	0.39
" Furthermore, the robust stimulating effects on normal and dyskinetic movements had an identical time course and parallel dose-response curves."	( Parallel dopamine D1 receptor activity dependence of l-Dopa-induced normal movement and dyskinesia in mice. Li, L; Zhou, FM, 2013)	0.39
" Different dosage of levodopa did not impact on the rotarod time (p>0."	( Anti-allodynic effects of levodopa in neuropathic rats. Joo, HS; Kim, ES; Kim, YH; Kwon, OK; Lee, J; Moon, DE; Park, HJ, 2013)	1.01
" Effects of escalating ropinirole dosage on plasma AVP levels were evaluated using a one-way analysis of variance for repeated measures, an a priori Dunnett multiple comparison test, and a regression analysis."	( Ropinirole does not affect plasma arginine vasopressin levels in patients with advanced Parkinson's disease. Arai, M, 2012)	0.38
" There was no statistically significant dose-response relationship between the ropinirole dosage and plasma AVP levels."	( Ropinirole does not affect plasma arginine vasopressin levels in patients with advanced Parkinson's disease. Arai, M, 2012)	0.38
"A minimal therapeutic dosage of ropinirole did not affect plasma AVP levels in patients with PD taking levodopa."	( Ropinirole does not affect plasma arginine vasopressin levels in patients with advanced Parkinson's disease. Arai, M, 2012)	0.59
"Extended-release carbidopa-levodopa might be a useful treatment for patients with Parkinson's disease who have motor fluctuations, with potential benefits including decreased off-time and reduced levodopa dosing frequency."	( Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial. Espay, AJ; Gupta, S; Hauser, RA; Hsu, A; Kell, S; O'Connell, M; Ondo, W; Sethi, K; Stacy, M, 2013)	0.98
"We determined LD, 3-OMD, and homocysteine plasma concentrations in relation to daily LD dosage administered orally or as duodenal infusion with and without vitamins."	( Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease. Jugel, C; Klostermann, F; Muhlack, S; Müller, T, )	0.13
" The same 3-OMD and homocysteine accumulation despite the applied higher LD dosage during the infusion indicates a limited methylation capacity."	( Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease. Jugel, C; Klostermann, F; Muhlack, S; Müller, T, )	0.13
" The full analysis set (FAS) comprised 564 patients (106 de novo; 458 pretreated [454 had complete rotigotine dosing data])."	( Effectiveness and tolerability of rotigotine transdermal patch for the treatment of restless legs syndrome in a routine clinical practice setting in Germany. Bachmann, CG; Berg, D; Berkels, R; Grieger, F; Hofmann, WE; Lauterbach, T; Schollmayer, E; Stiasny-Kolster, K, 2013)	0.39
" However, in particular, high levodopa dosing may contribute to disease progression."	( Detoxification and antioxidative therapy for levodopa-induced neurodegeneration in Parkinson's disease. Müller, T, 2013)	0.94
" To test this hypothesis in a rodent model, the A2A receptor antagonists SCH 412348 (3 mg/kg), vipadenant (10 mg/kg), caffeine (30 mg/kg), or istradefylline (3 mg/kg) were chronically (19-22 days) administered to Sprague Dawley rats, and dyskinetic behaviors were scored across this chronic dosing paradigm."	( A2A receptor antagonists do not induce dyskinesias in drug-naive or L-dopa sensitized rats. Bleickardt, C; Hodgson, R; Jones, N; Mullins, D; Parker, E, 2013)	0.39
" Based on final actual doses, there was a dose-response relationship on the modified Abnormal Involuntary Movements Scale, with 200 mg daily demonstrating the most robust effect (difference, -3."	( AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week, randomized, dose-finding study. Destee, A; Gao, H; Graf, A; Hattori, N; Hauser, RA; Kenney, C; Lang, AE; Merschhemke, M; Nagel, J; Poewe, W; Rascol, O; Stacy, M; Stocchi, F; Tolosa, E; Trenkwalder, C, 2013)	0.67
" The Unified Parkinson's Disease Rating Scale scores, TCM symptoms scores, quality of life, change of Madopar's dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period."	( Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial. Ma, YZ; Shen, XM; Zhang, J, 2013)	0.39
" After a washout period, repeat TC-8831 dosing led to a greater decline in LIDs (60%) in both sets of monkeys that was similar to the effect of nicotine."	( Nicotinic receptor agonists reduce L-DOPA-induced dyskinesias in a monkey model of Parkinson's disease. Bencherif, M; Carroll, FI; Letchworth, S; Mallela, A; Quik, M; Sohn, D; Zhang, D, 2013)	0.39
" L-dopa dosage and part IV of the UPDRS correlated with PDSS scores but not with polysomnographic parameters."	( Negative influence of L-dopa on subjectively assessed sleep but not on nocturnal polysomnography in Parkinson's disease. Antczak, JM; Banach, M; Derejko, M; Jakubczyk, T; Jernajczyk, W; Rakowicz, MJ; Sienkiewicz, J; Więcławska, M; Zalewska, U, 2013)	0.39
"The degree of reduction in presynaptic dopaminergic uptake at baseline is associated with higher antiparkinson drug dosage at follow-up, but the wide variation means that the baseline FP-CIT SPECT does not reliably predict drug use in individual cases."	( Baseline [(123) I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use at 3 years in Parkinson's disease. Grosset, DG; Grosset, KA; Hadley, D; Malek, N; Newman, EJ; Nissen, T; Patterson, J, 2014)	0.4
" Mavoglurant (AFQ056) was up-titrated over two weeks from 25 mg twice daily (bid) to 100 mg bid (L-dopa kept stable), followed by three weeks during which the daily L-dopa dosage was increased by up to 300 mg/day."	( Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson's disease patients. Dronamraju, N; Graf, A; Hauser, RA; Kenney, C; Kumar, R; Merschhemke, M; Mostillo, J, 2016)	0.69
" Moreover, no dose-response effect of levodopa on metabolic risk factors was observed."	( Cardiometabolic factors and disease duration in patients with Parkinson's disease. Barichella, M; Caccialanza, R; Cancello, R; Cassani, E; Cereda, E; Cilia, R; Madio, C; Pezzoli, G; Zini, M, )	0.4
" Dopaminergic pharmacotherapy and individual gene polymorphisms can affect the mesolimbic and prefrontal cortical dopaminergic functions in a comparable, inverted-U dose-response relationship."	( Dopamine overdose hypothesis: evidence and clinical implications. Bohnen, NI; Kwak, Y; Schonfeld, D; Seidler, R; Vaillancourt, DE, 2013)	0.39
"Fractionation of daily levodopa dosage is one strategy to manage the almost inevitable development of symptom fluctuations in Parkinson's disease (PD)."	( Levodopa fractionation in Parkinson's disease. Nyholm, D; Stepien, V, 2014)	2.16
"Fractionation of levodopa dosage into >4 daily doses was common."	( Levodopa fractionation in Parkinson's disease. Nyholm, D; Stepien, V, 2014)	2.18
" Initially, the l-DOPA dosing paradigm was evaluated."	( Effects of l-DOPA pre-loading on the uptake of boronophenylalanine using the F98 glioma and B16 melanoma models. Barth, RF; Chandra, S; Haider, SA; Huo, T; Kabalka, GW; Shaikh, AL; Yang, W, 2014)	0.4
" D1-like receptor activation produced an inverted U-shaped dose-response curve on plasticity induced by both facilitatory tDCS and PAS."	( Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans. Fresnoza, S; Kuo, MF; Nitsche, MA; Paulus, W, 2014)	0.4
" Further evaluations of optimal dosage and long-term efficacy and safety of metabotropic glutamate 5-receptor antagonists for management of L-Dopa-induced dyskinesias in Parkinson's disease are required."	( Use of metabotropic glutamate 5-receptor antagonists for treatment of levodopa-induced dyskinesias. Di Paolo, T; Fox, S; Gasparini, F; Gomez-Mancilla, B; Kenney, C; Rascol, O, 2014)	0.64
" A potential strategy, currently under investigation, is the coadministration of metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) and L-DOPA; a treatment that results in the improvement of dyskinesia symptoms and that permits reductions in l-DOPA dosage frequency."	( Mavoglurant as a treatment for Parkinson's disease. Auladell, C; Beas-Zarate, C; Camins, A; Canudas, AM; de Lemos, ML; Folch, J; Lazarowski, A; Pallàs, M; Pedros, I; Petrov, D, 2014)	0.4
" Staff familiarity with Parkinson disease, and especially carbidopa-levodopa dosing and dynamics, may prevent such problems and streamline hospital and nursing home care."	( Parkinson disease treatment in hospitals and nursing facilities: avoiding pitfalls. Ahlskog, JE, 2014)	0.64
" It is established that the antidyskinetic effect of the injectable dosage form of a new antiparkinsonian drug hemantane (5 mg/kg) after a single intravenous administration is weaker than that of the most effective in clinical practice antidyskinetic drug amantadine (20 mg/kg)."	( [Influence of hemantane in injectable dosage form on levodopa-induced dyskinesia in rats with model parkinsonian syndrome]. Ivanova, EA; Kapitsa, IG; Kokshenev, II; Nepoklonov, AV; Val'dman, EA; Voronina, TA, 2014)	0.65
" A dose-response study (0."	( The α7 nicotinic receptor agonist ABT-107 decreases L-Dopa-induced dyskinesias in parkinsonian monkeys. Decker, MW; McGregor, M; Quik, M; Zhang, D, 2014)	0.4
" Age, polypharmacy, change of one-year daily levodopa equivalent dosage and newly onset of dementia, stroke and psychiatric diseases all affect drug compliance in PD patients."	( Initial medication in patients of newly diagnosed Parkinson's disease in Taiwan. Chang, MH; Guo, YJ; Liao, YC; Lin, CH, 2014)	0.66
" Their median daily LD dosage was 1495 mg from IPX066 and 600 mg from CL + E, corresponding, after correction for bioavailability, to an approximately 22% higher LD exposure on IPX066."	( Comparison of IPX066 with carbidopa-levodopa plus entacapone in advanced PD patients. Dillmann, U; Ellenbogen, A; Gupta, S; Hsu, A; Kell, S; Khanna, S; Liang, G; Mahler, A; Rubens, R; Stocchi, F, 2014)	0.68
" However, the dosage and the actual effectiveness of carbidopa have not yet been well defined."	( Evaluation of levodopa and carbidopa antioxidant activity in normal human lymphocytes in vitro: implication for oxidative stress in Parkinson's disease. Ceci, R; Colamartino, M; Cozzi, R; Duranti, G; Padua, L; Sabatini, S; Santoro, M; Testa, A, 2015)	0.78
" The distribution of difference NMS is associated with the severity of motor symptoms and the dosage of anti-PD medications in Chinese PD patients."	( The heterogeneity of non-motor symptoms of Parkinson's disease. Cohen, AD; Liu, W; Ye, M; Zhang, N; Zhang, Y, 2015)	0.42
" The two formulations are bioequivalent; the majority (>80 %) of patients can be switched overnight from pramipexole IR to ER without the need for dosage adjustment."	( Pramipexole extended-release: a review of its use in patients with Parkinson's disease. Frampton, JE, 2014)	0.4
" Both patients exhibited the clinical features of serotonin syndrome, coinciding with an increase in dosage of each drug."	( Serotonin syndrome in stroke patients. Chang, MC; Jang, SH; Kwon, YM, 2015)	0.42
" In early PD, this may avoid dose escalation or allow a reduction in dopamine agonist dosage without a loss of efficacy and prevent dopaminergic side-effects from becoming treatment limiting."	( The adenosine A2A receptor antagonist, istradefylline enhances the anti-parkinsonian activity of low doses of dopamine agonists in MPTP-treated common marmosets. Jenner, P; Kanda, T; Kawai-Uchida, M; Mori, A; Okita, E; Soshiroda, K; Uchida, S, 2015)	0.42
"The objective of this study was to investigate the risk factors of wearing-off phenomenon in Parkinson's disease (PD) and propose safe dosage of levodopa to reduce wearing-off development based on Chinese cohort."	( Risk factors and safe dosage of levodopa for wearing-off phenomenon in Chinese patients with Parkinson's disease. Chen, H; Fang, J; Feng, T; Gao, L; Li, F, 2015)	0.9
"The major modifications in medication dosage occurred during the initial postoperative period."	( The medical treatment of patients with Parkinson's disease receiving subthalamic neurostimulation. Alexoudi, A; Deuschl, G; Knudsen, K; Mehdorn, M; Shalash, A; Volkmann, J; Witt, K, 2015)	0.42
"STN-DBS allows for a reduction in the dosage of medication and the costs are similarly reduced."	( The medical treatment of patients with Parkinson's disease receiving subthalamic neurostimulation. Alexoudi, A; Deuschl, G; Knudsen, K; Mehdorn, M; Shalash, A; Volkmann, J; Witt, K, 2015)	0.42
"Thirty-four patients were enrolled; mean baseline L-dopa dosage was 968 mg/d."	( Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced Parkinson's disease. Chen, C; Cowles, VE; Stover, N; Sweeney, M; Verhagen Metman, L, 2015)	0.72
"DM-1992 was associated with a reduction in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency."	( Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced Parkinson's disease. Chen, C; Cowles, VE; Stover, N; Sweeney, M; Verhagen Metman, L, 2015)	0.72
" Dosage of levodopa and oral DA (pramipexole ≤1."	( Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinson's disease: an open-label study. Bauer, L; Chung, SJ; Ikeda, J; Jeon, BS; Kim, JM; Kim, JW; Singh, P; Thierfelder, S, 2015)	0.81
" Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies."	( Long-Term Treatment with Extended-Release Carbidopa-Levodopa (IPX066) in Early and Advanced Parkinson's Disease: A 9-Month Open-Label Extension Trial. Dzyak, L; Gupta, S; Hsu, A; Kell, S; Khanna, S; Nausieda, P; Rudzinska, M; Silver, DE; Spiegel, J; Tsurkalenko, ES; Waters, CH, 2015)	0.67
"Clinical experience with 2 LCIG dosing paradigms from phase 3 studies was examined."	( Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials. Benesh, JA; Chatamra, K; Dubow, JS; Fung, VS; Krüger, R; Lew, MF; Martínez Castrillo, JC; Robieson, WZ; Slevin, JT, 2015)	0.69
"6 days; dosing remained stable post-titration (mean total daily dose [TDD] was 1572 mg at last visit)."	( Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials. Benesh, JA; Chatamra, K; Dubow, JS; Fung, VS; Krüger, R; Lew, MF; Martínez Castrillo, JC; Robieson, WZ; Slevin, JT, 2015)	0.69
" Interestingly, plasma taurine levels negatively correlated with cumulative levodopa dosage in tPD."	( Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment. Ding, J; Jiang, S; Tong, Q; Xu, Q; Yuan, Y; Zhang, K; Zhang, L; Zhang, R, 2016)	0.89
" An increase of the levodopa dosage led to clinical improvement, which needed a maintenance dosage because of dependency."	( Parkinsonism Improved With Levodopa After Endoscopic Third Ventriculostomy in Shunted Hydrocephalus Due to Aqueductal Stenosis. Endo, T; Nakazawa, M; Ohnishi, H; Okawa, S; Sanpei, Y; Sugawara, M, 2015)	1.04
" The in vitro drug release of the delivery systems was compared to those of the conventional dosage forms and in vivo absorption was predicted."	( An optimized gastroretentive nanosystem for the delivery of levodopa. Choonara, YE; du Toit, LC; Kumar, P; Modi, G; Ngwuluka, NC; Pillay, V, 2015)	0.66
" Rats were dosed orally with Tozadenant, a selective A2A receptor antagonist, and three different doses of Radiprodil, an NR2B-selective NMDA receptor antagonist."	( Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA-Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non-Dopaminergic Drugs. De Wolf, C; Downey, P; Michel, A; Scheller, D; Schwarting, R; Van Damme, X, 2015)	0.42
" Voxelwise one-way analysis of covariance and post hoc analyses of ALFF were performed among the three groups, with age and gender as covariates (levodopa daily dosage and gray matter volume as additional covariates for validation analysis)."	( Different patterns of spontaneous brain activity between tremor-dominant and postural instability/gait difficulty subtypes of Parkinson's disease: a resting-state fMRI study. Chen, HM; Fang, JP; Feng, T; Gao, LY; Hou, YN; Ma, LY; Wang, ZJ; Wu, T; Zhang, JR, 2015)	0.62
" IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours."	( Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. Elmer, L; Gil, RA; Gupta, S; Hsu, A; Kell, S; Khanna, S; Modi, NB; Nausieda, PA; Rubens, R; Singer, C; Spiegel, J, 2015)	0.69
"To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting."	( Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. Elmer, L; Gil, RA; Gupta, S; Hsu, A; Kell, S; Khanna, S; Modi, NB; Nausieda, PA; Rubens, R; Singer, C; Spiegel, J, 2015)	0.69
" Suggested initial dosing conversion tables based on prior LD daily dosage were provided."	( Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. Elmer, L; Gil, RA; Gupta, S; Hsu, A; Kell, S; Khanna, S; Modi, NB; Nausieda, PA; Rubens, R; Singer, C; Spiegel, J, 2015)	0.69
" A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model."	( Dose-Response Analysis of the Effect of Carbidopa-Levodopa Extended-Release Capsules (IPX066) in Levodopa-Naive Patients With Parkinson Disease. Mao, ZL; Modi, NB, 2016)	0.93
"The addition of opicapone 50 mg to levodopa treatment in patients with Parkinson's disease and end-of-dose motor fluctuations could enable a simplified drug regimen that allows physicians to individually tailor the existing levodopa daily regimen, by potentially reducing the total daily levodopa dose, increasing the dosing interval, and ultimately reducing the number of intakes, thereby maximising its benefit."	( Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Ferreira, JJ; Lees, A; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P, 2016)	1.01
" Levodopa/carbidopa intestinal gel is an aqueous gel that can be delivered to the jejunum via a percutaneous gastrojejunostomy tube which is connected to an infusion pump dosing the levodopa gel continuously to the place of absorption."	( [Application of levodopa/carbidopa intestinal gel in advanced Parkinson's disease]. Bereczki, D; Nagy, H; Takáts, A; Toth, A; Wacha, J, 2015)	1.67
" After this dosing change, the patient failed to develop fever during the rest of his hospital stay."	( Levodopa Withdrawal Presenting as Fever in a Critically Ill Patient Receiving Concomitant Enteral Nutrition. Ablordeppey, E; Taylor, B; Whitman, CB, 2016)	1.88
" Facial emotion recognition was measured twice during target LCE dosing and twice on placebo: once without cocaine and once after repeated cocaine doses."	( Effects of levodopa-carbidopa-entacapone and smoked cocaine on facial affect recognition in cocaine smokers. Bedi, G; Bisaga, A; Foltin, RW; Nunes, EV; Shiffrin, L; Vadhan, NP, 2016)	0.82
" While fractionation of levodopa dosage is the most frequently utilized strategy, many patients require deep brain stimulation to control their troublesome motor fluctuations and LIDs."	( Drug-Induced Dyskinesia, Part 1: Treatment of Levodopa-Induced Dyskinesia. Jankovic, J; Vijayakumar, D, 2016)	1
" It is critical to understand the appropriate conversion of the carbidopa/levodopa daily dosages to the CLES dosage and how to program the pump and titrate CLES to achieve the most effective dose."	( Outpatient titration of carbidopa/levodopa enteral suspension (Duopa). Lyons, KE; Pahwa, R, 2017)	0.97
"  Madopar dosage was maintained in both groups."	( The effect of levodopa benserazide hydrochloride on homocysteinemia levels in patients with Parkinson's disease and treatment of hyperhomocysteinemia. Cao, LD; Guo, G; Wu, QY; Xu, S, 2016)	0.79
" Its dosage requires careful monitoring, since the required amount changes over time, and excess dosage can lead to muscle spasms known as levodopa-induced dyskinesia."	( Using epigenetic networks for the analysis of movement associated with levodopa therapy for Parkinson's disease. Alty, JE; Cosgrove, J; Jamieson, S; Lones, MA; Smith, SL; Trefzer, MA; Turner, AP; Tyrrell, AM, 2016)	0.87
" Compared with STN DBS, increased dosage of levodopa equivalent doses was needed in GPi DBS (standardized MD =0."	( Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson's disease: a meta-analysis of randomized controlled trials. Huang, T; Jiang, Y; Tan, ZG; Zhou, Q, 2016)	0.7
" Meanwhile, GPi DBS was also associated with increased dosage of levodopa equivalent doses."	( Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson's disease: a meta-analysis of randomized controlled trials. Huang, T; Jiang, Y; Tan, ZG; Zhou, Q, 2016)	0.67
" Patients presented to clinic in the morning in the practically defined OFF state and were dosed with APL-130277 10 mg."	( Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson's disease. Agro, A; Bilbault, T; Dubow, J; Dzyngel, B; Hauser, RA; Isaacson, S; Olanow, CW; Shill, H, 2016)	0.43
" Moreover, pseudoresistance can emerge as not all features of PD respond adequately to the same dosage of levodopa."	( Unmasking levodopa resistance in Parkinson's disease. Bloem, BR; de Vries, NM; Helmich, RC; Nonnekes, J; Rascol, O; Timmer, MH, 2016)	1.05
" In addition, the association between premotor symptoms and levodopa equivalent dosage (LED) was examined."	( Premotor Symptoms as Predictors of Outcome in Parkinsons Disease: A Case-Control Study. Chang, MH; Chen, YH; Lee, WJ; Lin, CH; Wu, YH, 2016)	0.68
" Case-control analysis revealed that male, initial extremity of motor symptom onset, history of depressive disorder, delusion, any psychiatric disorder, and higher L-dopa dosage were significantly associated with suicide among PD patients."	( Increased suicide risk and clinical correlates of suicide among patients with Parkinson's disease. Ahn, MH; Chung, SJ; Hong, JP; Kim, J; Kim, MS; Lee, HB; Lee, T, 2016)	0.43
"5 min after administration; in contrast, in dogs dosed orally with levodopa plus carbidopa, plasma levodopa was not detected until 30 min after administration."	( Preclinical and clinical assessment of inhaled levodopa for OFF episodes in Parkinson's disease. Batycky, R; Freed, MI; Leinonen, M; Lipp, MM; Moore, J, 2016)	0.93
"On the whole, after switching from "pulsatile" to "pulse" administration, there was a reduction in number of L-dopa daily doses and an increase in the amount of the dosage of the single doses, AIMS maximum score decreased without increasing motor disability."	( Switching L-dopa Therapy from Pulsatile to Pulse Administration Reduces Motor Complications in Parkinson's Disease. Cicero, CE; Contrafatto, D; Dibilio, V; Donzuso, G; Luca, A; Mostile, G; Nicoletti, A; Raciti, L; Sciacca, G; Vasta, R; Zappia, M, )	0.13
" Therefore, the dosage of dopa-decarboxylase inhibitor, increasing the L-dopa concentration, may contribute to GE delay and its consequent effect on drug delivery and efficacy."	( Delayed Gastric Emptying in Advanced Parkinson Disease: Correlation With Therapeutic Doses. Bestetti, A; Capozza, A; Lacerenza, M; Mancini, F; Manfredi, L, 2017)	0.46
"This phase 3 international, multicenter outpatient study evaluated a 25- and a 50-mg/d dosage of opicapone in a randomized, double-blind, 14- to 15-week, placebo-controlled clinical trial, followed by a 1-year open-label phase during which all patients received active treatment with opicapone."	( Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. Ferreira, J; Lees, AJ; McCrory, M; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P, 2017)	0.76
"8] years) were randomized to a 25-mg/d (n = 129) or a 50-mg/d (n = 154) dosage of opicapone or to placebo (n = 144)."	( Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. Ferreira, J; Lees, AJ; McCrory, M; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P, 2017)	0.76
" Examples and a case study to illustrate how pharmacokinetics and pharmacodynamics contributed to the selection of dosing regimens, demonstration of an improved therapeutic effect, or regulatory approval of an improved product label are presented."	( Application of Pharmacokinetics and Pharmacodynamics in Product Life Cycle Management. A Case Study with a Carbidopa-Levodopa Extended-Release Formulation. Modi, NB, 2017)	0.66
"This Phase IV, double-blind, randomized, parallel-group study characterized the dose-response and tolerability of fixed doses of ropinirole prolonged release (PR) in subjects with advanced Parkinson's disease."	( A randomized, fixed-dose, dose-response study of ropinirole prolonged release in advanced Parkinson's disease. Chriscoe, S; Davy, M; Jimenez, T; Upward, J; VanMeter, S; Zesiewicz, TA, 2017)	0.46
"IPX066 (Rytary®; carbidopa and levodopa [CD-LD] extended-release capsules) was designed to achieve therapeutic LD plasma concentrations within 1h of dosing and maintain LD concentrations for a prolonged duration in early or advanced Parkinson's disease (PD)."	( Conversion to carbidopa and levodopa extended-release (IPX066) followed by its extended use in patients previously taking controlled-release carbidopa-levodopa for advanced Parkinson's disease. Duker, AP; Ellenbogen, A; Farbman, ES; Gupta, S; Hauser, RA; Hsu, A; Kell, S; Khanna, S; Kreitzman, D; Liang, GS; Nausieda, P; Nieves, A; Rubens, R; Tetrud, J, 2017)	1.04
" Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall."	( Levodopa, placebo and rotigotine change biomarker levels for oxidative stress. Herrman, L; Kinkel, M; Muhlack, S; Müller, T, 2017)	2.41
"To evaluate individualized levodopa/carbidopa dosing using microtablets dispensed with a dose dispenser, with respect to efficacy and usability as perceived by patients."	( First clinical experience with levodopa/carbidopa microtablets in Parkinson's disease. Albo, J; Hellström, M; Nyholm, D; Senek, M; Svenningsson, P, 2017)	1.04
" Safinamide will help to reduce dosing of levodopa but also of dopamine agonists during long term treatment in patients with Parkinson's disease."	( Pharmacokinetic drug evaluation of safinamide mesylate for the treatment of mid-to-late stage Parkinson's disease. Müller, T, 2017)	0.72
"Correlation analysis showed that age, gender, education, disease duration, Hohn-Yahr stage, UPDRS-II and UPDRS-III scores, and dosage of levodopa do not correlate with the daily movement function (P > 0."	( Continuous quantitative monitoring of physical activity in Parkinson's disease patients by using wearable devices: a case-control study. Cai, G; Dai, H; Huang, Y; Lin, Z; Luo, S; Ye, Q, 2017)	0.66
" Although levodopa remains the single effective agent in the management of Parkinson's disease, the accurate determination of this optimal dosage is complicated by marked between-subject and between-occasion variability in this population."	( Levodopa in Parkinson's Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis. Azulay, JP; Blin, O; Guilhaumou, R; Marsot, A, 2017)	2.3
" A detailed understanding of the nature of PD-specific gastrointestinal parameters and of how they may affect drug release of orally administered dosage forms seems to be essential information for developing better oral PD medications."	( A review of patient-specific gastrointestinal parameters as a platform for developing in vitro models for predicting the in vivo performance of oral dosage forms in patients with Parkinson's disease. Klein, S; Wollmer, E, 2017)	0.46
" The primary outcome of this study was to assess the postoperative improvement in the symptoms, evaluated using either Unified Parkinson's Disease Rating Scale (UPDRS) scores or levodopa equivalent dosage (LEDD) requirement."	( Comparison of General and Local Anesthesia for Deep Brain Stimulator Insertion: A Systematic Review. Englesakis, M; Manninen, P; Mehta, J; Rowland, NC; Sheshadri, V; Venkatraghavan, L, 2017)	0.65
" Regarding the clinical outcomes, there were no significant differences in the postoperative Unified Parkinson's disease rating scale and levodopa equivalent drug dosage between the GA and the LA groups."	( Comparison of General and Local Anesthesia for Deep Brain Stimulator Insertion: A Systematic Review. Englesakis, M; Manninen, P; Mehta, J; Rowland, NC; Sheshadri, V; Venkatraghavan, L, 2017)	0.66
" Collectively, this data highlights the importance of the frontal cortex in methamphetamine-induced effects, and also the similar dose-response effect of methamphetamine on dopamine and BDNF expression."	( Dose-Dependent Effects of Binge-Like Methamphetamine Dosing on Dopamine and Neurotrophin Levels in Rat Brain. Doyle, KM; Kelly, JP; Moreira da Silva Santos, A, 2017)	0.46
" No difference was observed in maintenance dosage of rotigotine between the two groups."	( Efficacy and safety of rotigotine in elderly patients with Parkinson's disease in comparison with the non-elderly: a post hoc analysis of randomized, double-blind, placebo-controlled trials. Iwaki, H; Kondo, H; Nomoto, M; Sakurai, M, 2018)	0.48
" The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients."	( Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients. Bartošová, O; Bonnet, C; Perlík, F; Růžička, E; Šíma, M; Slanař, O; Ulmanová, O, 2018)	0.48
" This study describes an algorithmic method to derive optimized dosing suggestions for infusion treatment of PD, by fitting individual dose-response models."	( Individual dose-response models for levodopa infusion dose optimization. Alam, M; Nyholm, D; Senek, M; Thomas, I; Westin, J, 2018)	0.76
"Patient records were collected at Uppsala University hospital which provided dosing information and dose-response evaluations."	( Individual dose-response models for levodopa infusion dose optimization. Alam, M; Nyholm, D; Senek, M; Thomas, I; Westin, J, 2018)	0.76
" To our knowledge, this study is the first to explore the potential of unsupervised technology-based objective motor and non-motor tasks to monitor subacute LD dosing effects in PD patients."	( Supervised versus unsupervised technology-based levodopa monitoring in Parkinson's disease: an intrasubject comparison. Calandra-Buonaura, G; Chiari, L; Contin, M; Cortelli, P; Corzani, M; Lopane, G; Mellone, S, 2018)	0.74
" We aim to determine the motor improvement and reduction in medication dosage of all patients with PD who underwent DBS at the Philippine Movement Disorder Surgery Center."	( Deep Brain Stimulation for Parkinson Disease in the Philippines: Outcomes of the Philippine Movement Disorder Surgery Center. Aguilar, JA; Anlacan, JP; Diestro, JDB; Jamora, RDG; Teleg, RA; Vesagas, TS, 2018)	0.48
" A significant reduction in the dosage of PD medications was also seen until the second year of follow-up (52."	( Deep Brain Stimulation for Parkinson Disease in the Philippines: Outcomes of the Philippine Movement Disorder Surgery Center. Aguilar, JA; Anlacan, JP; Diestro, JDB; Jamora, RDG; Teleg, RA; Vesagas, TS, 2018)	0.48
"DBS for PD improves the UPDRS motor score in the off-medication and on-medication state, with the maximal benefit seen at 3 years after surgery and reduces PD medication dosage by half."	( Deep Brain Stimulation for Parkinson Disease in the Philippines: Outcomes of the Philippine Movement Disorder Surgery Center. Aguilar, JA; Anlacan, JP; Diestro, JDB; Jamora, RDG; Teleg, RA; Vesagas, TS, 2018)	0.48
"Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal."	( Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms. Hoppe, M; Koziolek, M; Schneider, F; Weitschies, W, 2018)	0.48
" The levodopa equivalent dosage did not change."	( A High-Intensity Multicomponent Agility Intervention Improves Parkinson Patients' Clinical and Motor Symptoms. Hortobágyi, T; Kovács, N; Nagy, F; Tollár, J, 2018)	0.99
" While there is some evidence that anti-parkinsonian medication, levodopa, might not improve balance and gait control or reduce fall risk in the PIGD subtype, it is unclear whether the levodopa dosage intake affects gait stability."	( Head and trunk stability during gait before and after levodopa intake in Parkinson's disease subtypes. Brodie, MA; Fung, VSC; Latt, MD; Lord, SR; Menant, JC; Menz, HB; Pelicioni, PHS, 2018)	0.97
" To reduce the daily dosing of L-DOPA in patients, inhibitors of dopamine catabolizing enzymes, particularly monoamine oxidase-B (MAO-B), are prescribed."	( Garcinol, an effective monoamine oxidase-B inhibitor for the treatment of Parkinson's disease. Bhattacharya, P; Borah, A; Chakrabarty, J; Dutta, A; Mazumder, MK; Paul, R; Phukan, BC, 2018)	0.48
" Several factors hamper the use of current available catechol-O-methyl transferase inhibitors, that is, the moderate efficacy and multiple dosing for entacapone and the risk of liver toxicity with tolcapone."	( Opicapone for the treatment of Parkinson's disease: A review of a new licensed medicine. Fabbri, M; Ferreira, JJ; Lees, A; Poewe, W; Rascol, O; Stocchi, F; Tolosa, E, 2018)	0.48
" Therefore, it is critical to control the levodopa dosage accuracy to improve the curative effect in clinical."	( Smartphone-based differential pulse amperometry system for real-time monitoring of levodopa with carbon nanotubes and gold nanoparticles modified screen-printing electrodes. Cheng, C; Ji, D; Liu, J; Liu, Q; Liu, Z; Low, SS; Shi, Z; Xu, H; Xu, N; Yu, X; Zhang, T; Zhu, J, 2019)	1
"A new extended release levodopa capsule (C/L ERC), Rytary®, has demonstrated improved "on" time in fluctuating Parkinson's disease patients, compared to optimally dosed immediate release levodopa."	( Conversion of L-dopa to Extended Release L-dopa (Rytary®) in Patients with Fluctuating Parkinson's Disease: Predictors of Dose. Christie, M; Coss, P; Ondo, W; Pascual, B, 2019)	0.82
" Mayo neurologists favoring levodopa dosage optimization treated most patients."	( Levodopa-induced dyskinesia in Parkinson disease: A population-based cohort study. Ahlskog, JE; Bower, JH; Cutsforth-Gregory, JK; Mielke, MM; Parisi, JE; Savica, R; Turcano, P, 2018)	2.22
" Motor response to and pre-surgical dosage of levodopa, male gender, and shorter PD duration were identified as predictors for posture improvement after STN DBS."	( Effect of subthalamic deep brain stimulation on posture in Parkinson's disease: A blind computerized analysis. Artusi, CA; Boyne, P; Espay, AJ; Fasano, A; Lopiano, L; Merola, A; Roediger, J; Romagnolo, A; Zibetti, M, 2019)	0.77
" Our results highlight the role of microbial metabolism in drug availability, and specifically, that abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen of levodopa treatment in Parkinson's disease patients."	( Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Castejon, M; El Aidy, S; El-Gendy, AO; Frye, AK; Keshavarzian, A; van Dijk, G; van Kessel, SP, 2019)	0.94
" This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS)."	( Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease: a first experience. Alam, M; Bergquist, F; Johansson, D; Memedi, M; Nyholm, D; Thomas, I; Westin, J, 2019)	0.98
" The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm."	( Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease: a first experience. Alam, M; Bergquist, F; Johansson, D; Memedi, M; Nyholm, D; Thomas, I; Westin, J, 2019)	0.75
"This study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients."	( Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease: a first experience. Alam, M; Bergquist, F; Johansson, D; Memedi, M; Nyholm, D; Thomas, I; Westin, J, 2019)	0.75
" The classical symptomatic treatment for PD is Levodopa (L-DOPA) which brings a plethora of side effects and dosage problems in a prolonged drug regimen."	( Baicalein enhances the effect of low dose Levodopa on the gait deficits and protects dopaminergic neurons in experimental Parkinsonism. Bian, ZX; Chan, HY; Cheung, CY; Li, Y; Lyu, H; Poon, WS; Wang, KKW; Zheng, ZV, 2019)	1.04
" This study aimed to examine the performance of TRIS for medication effects in a new population sample with Parkinson's disease (PD) and its usefulness for constructing individual dose-response models."	( Evaluation of a sensor algorithm for motor state rating in Parkinson's disease. Bergquist, F; Ericsson, A; Johansson, A; Johansson, D; Medvedev, A; Memedi, M; Nyholm, D; Ohlsson, F; Senek, M; Spira, J; Thomas, I; Westin, J, 2019)	0.51
"The objective sensor index shows promise for constructing individual dose-response models, but further evaluations and retraining of the TRIS algorithm are desirable to improve its performance and to ensure its clinical effectiveness."	( Evaluation of a sensor algorithm for motor state rating in Parkinson's disease. Bergquist, F; Ericsson, A; Johansson, A; Johansson, D; Medvedev, A; Memedi, M; Nyholm, D; Ohlsson, F; Senek, M; Spira, J; Thomas, I; Westin, J, 2019)	0.51
" Using a randomized, double-blind, 2-way crossover design, eligible patients in the morning OFF state (having not received PD medication overnight) received a single dose of CVT-301 84 mg or placebo on 2 dosing days, immediately after their first morning oral carbidopa/levodopa dose."	( Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson's disease. Ellenbogen, A; Hauser, RA; Isaacson, SH; Kegler-Ebo, DM; Komjathy, SF; Oh, C; Safirstein, BE; Truong, DD; Zhao, P, 2019)	1.05
" Adult Wistar rats treated with CPZ (3 mg/kg/day, IP) were orally dosed with diclofenac and L-dopa/carbidopa for 21 days."	( Neuroprotective effect of diclofenac on chlorpromazine induced catalepsy in rats. Khan, SS; Mirza, T; Naeem, S; Najam, R; Sikandar, B, 2019)	0.51
"This series of studies demonstrates that small continuous dosing of subcutaneous CD has an unexpected effect on LD pharmacokinetics greater than the extent of decarboxylase inhibition achieved by additional oral CD administration."	( Subcutaneous Administration of Carbidopa Enhances Oral Levodopa Pharmacokinetics: A Series of Studies Conducted in Pigs, Mice, and Healthy Volunteers. Caraco, Y; LeWitt, PA; Nemas, M; Oren, S; Shaltiel-Karyo, R; Weinstock, I; Yacoby-Zeevi, O; Zawaznik, E, )	0.38
" We investigated possible predictive factors for the successful reduction of antiparkinsonian drug dosage after STN-DBS."	( Predictive Factors of Antiparkinsonian Drug Reduction after Subthalamic Stimulation for Parkinson's Disease. Kawaguchi, M; Kawashima, M; Miyagi, Y; Okamoto, T; Samura, K; Yoshida, F, 2019)	0.51
"Changing drug dosage is common in clinical practice."	( Verbal communication about drug dosage balances drug reduction in Parkinson's disease: Behavioral and electrophysiological evidences. Benedetti, F; Carlino, E; Frisaldi, E; Guerra, G; Lopiano, L; Piedimonte, A; Romagnolo, A; Vighetti, S, 2019)	0.51
" In particular, the monitoring and optimization of levodopa dosage are critical to mitigate the onset of undesired fluctuations in the patients' physical and emotional conditions such as speech function, motor behavior, and mood stability."	( Wearable Sweat Band for Noninvasive Levodopa Monitoring. Bariya, M; Fan, Z; Hettick, M; Hou, L; Javey, A; Ji, W; Liaw, TS; Lin, Y; Nyein, HYY; Tai, LC; Yuan, Z; Zhao, C; Zhao, J, 2019)	1.04
" The design and attractive analytical performance of the new orthogonal wearable microneedle sensor array hold considerable promise for reliable, continuous, minimally invasive monitoring of L-Dopa in the ISF toward optimizing the dosing regimen of the drug and effective management of Parkinson disease."	( Wearable Electrochemical Microneedle Sensor for Continuous Monitoring of Levodopa: Toward Parkinson Management. Goud, KY; Litvan, I; Mishra, RK; Moonla, C; Narayan, R; Wang, J; Yu, C, 2019)	0.75
" As LD/BH sustained release suspension can synchronize sustained release of multiple active ingredients by oral administration, the suspension presents promising oral dosage forms for geriatric patients with PD."	( Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide. Ding, YP; Lai, WL; Liu, HF; Qu, Y; Wang, L; Xin, YR; Xu, Y; Zhu, FQ; Zhu, Y, 2019)	0.72
" Increasing the dosage of levodopa and prolonging the treatment can significantly improve the curative effect."	( Systematic Evaluation of Levodopa Effect on Visual Improvement in Amblyopia: A Meta-analysis. Li, QX; Li, S; Wang, SP, )	0.73
" Lower maximal force, higher unintentional force production (enslaving) and higher inter-trial variance indices occurred in PD patients after one dosage of levodopa."	( Synergic control of action in levodopa-naïve Parkinson's disease patients: I. Multi-finger interaction and coordination. Corson, T; de Freitas, PB; Freitas, SMSF; Huang, X; Latash, ML; Lewis, MM; Reschechtko, S, 2020)	1.04
" We chronically treated (over 6 months) mice lacking both chromogranins A and B (Cgs-KO) with a low oral dosage of L-DOPA/benserazide (10/2."	( Combining the lack of chromogranins with chronic L-DOPA treatment affects motor activity in mice. Borges, R; Castañeyra, A; Castañeyra-Ruiz, L; González-Santana, A; Machado, JD, 2020)	0.56
" Devices such as continuous infusion pumps and new dosage forms have been developed to improve the treatment response to L-dopa."	( [Current Status and Future Prospects of Therapeutic Development of Parkinson's Disease]. Mochizuki, H, 2020)	0.56
" Clinically, accurately and objectively assessing the severity of PD symptoms is critical in controlling appropriate dosage of Levodopa to prevent unwanted side effect of switching between Dyskinesia and PD."	( Improving Automatic Tremor and Movement Motor Disorder Severity Assessment for Parkinson's Disease with Deep Joint Training. Chang, CM; Chen, JC; Huang, YL; Lee, CC, 2019)	0.72
" Here, we present a lady with moderate PD and superimposed anxiety for whom this management strategy did not work well as it increased her anxiety significantly around dosing times."	( Patient-controlled variable dosing of levodopa for Parkinson's disease. Abdelhafiz, AH; Rose, J; Roycroft, M, 2020)	0.83
" Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days."	( A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia. Bergquist, F; Dizdar, N; Grigoriou, S; Hansson, F; Johansson, A; Nyholm, D; Odin, P; Rinne, J; Sonesson, C; Svenningsson, P; Tedroff, J; Tsitsi, P; Wictorin, K, 2020)	0.56
" Regression analysis showed a small, but significant relationship between levodopa and dopamine agonist dosage and total IGT score, indicating that medication level could be a marker of level of executive functions."	( Applied strategy in the Iowa Gambling Task: Comparison of individuals with Parkinson's disease to healthy controls. Borghammer, P; Callesen, MB; Damholdt, MF; Kjær, SW; Larsen, L; Østergaard, K, 2020)	0.79
" Compared to NBR patients, BR patients had relatively low body weight, low BMI, long disease duration, high levodopa equivalent daily dosage (LEDD), and high levodopa dose per weight (P < 0."	( Analysis of factors associated with brittle response in patients with Parkinson's disease. Chang, Y; Li, Y; Liu, X; Wang, L; Yan, Y; Zhang, L, 2020)	0.77
" Therapeutically, this in turn leads to further fractioning of the levodopa dosage and a reduction of single-dose levels."	( [New Therapeutic Options for the Individualised Titration of Levodopa]. Ebersbach, G; Jost, WH; Kassubek, J; Klebe, S; Tönges, L, 2021)	1.1
" Patients with OFD used significantly higher levodopa equivalent daily dosage (LEDD) than those without (p = 0."	( Orofacial dystonia and asssociated bulbar symptoms in multiple system atrophy: A blinded video analysis. Bhidayasiri, R; Panyakaew, P; Thongchuam, Y, 2020)	0.82
"As a vital therapeutic agent for Parkinson's disease, dosage control of levodopa has always been a major obstacle in ensuring efficacy and curbing side effects."	( Differential coulometry based on dual screen-printed strips for high accuracy levodopa determination towards Parkinson's disease management. Cai, Y; Cao, Q; Fang, L; Liang, B; Tu, T; Ye, X; Yu, C, 2020)	1.02
" Among PD patients, a clear and robust dose-response association was found between levodopa equivalent dose and UME, independent of potential confounding factors, including Parkinson's disease severity."	( Melatonin secretion in patients with Parkinson's disease receiving different-dose levodopa therapy. Kataoka, H; Kurumatani, N; Obayashi, K; Saeki, K; Sugie, K, 2020)	1.01
" This model paves the way toward individualization of a dosing regimen."	( Nonlinear pharmacodynamics of levodopa through Parkinson's disease progression. Lévesque, D; Nekka, F; Robaey, P; Ursino, M; Véronneau-Veilleux, F, 2020)	0.85
" However, using such data to overhaul the current static medication treatment planning approach and prescribe personalized medication timing and dosage that accounts for patient/care-giver/physician feedback/preferences remains an open question."	( Optimizing Individualized Treatment Planning for Parkinson's Disease Using Deep Reinforcement Learning. Khojandi, A; Ramdhani, R; Vasudevan, R; Watts, J, 2020)	0.56
"We found that the 10 mg/kg l-dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra."	( The Vasomotor Response to Dopamine Is Altered in the Rat Model of l-dopa-Induced Dyskinesia. Anderson, C; Booth, S; Jackson, MF; Kirouac, G; Ko, JH; Lu, L; Ramadan, A; Zhang, D, 2021)	0.62
"ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson's disease (PD) experiencing motor fluctuationsObjective:Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD."	( Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study. Adar, L; Case, RJ; Ellenbogen, AL; Espay, AJ; Leinonen, M; Olanow, CW; Oren, S; Orenbach, SF; Poewe, W; Stocchi, F; Yardeni, T, 2021)	1.2
" However, a U-shaped dose-response curve obtained with certain parameters may limit the therapeutic potential of this strategy and require further investigation."	( Granisetron, a selective 5-HT3 antagonist, reduces L-3,4-dihydroxyphenylalanine-induced abnormal involuntary movements in the 6-hydroxydopamine-lesioned rat. Bédard, D; Frouni, I; Hamadjida, A; Huot, P; Kwan, C, 2021)	0.62
"To overcome the problem of incorrect levodopa (LD) dosage in the treatment of Parkinson's disease, a new analytical tool is urgently needed for accurately determining the concentration of LD in human fluids."	( Single-atom electrocatalysts templated by MOF for determination of levodopa. Gao, M; Li, Y; Liang, W; Tong, Y; Ye, BC, 2021)	1.13
" Moreover, as the daily dosage of levodopa increased, the daily number of tablets increased for both overall anti-parkinsonian drugs and adjuvants to levodopa."	( [Prescribing Patterns for Anti-Parkinsonian Drugs in Japan: Prescription-Based Database Study]. Hattori, A; Ibe, S; Kinoshita, F; Maeda, T; Tsunekawa, K; Yamamoto, J, 2021)	0.9
" Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples."	( Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration. De la Paz, E; Huang, N; Litvan, I; Longardner, K; Mahato, K; Moon, JM; Sempionatto, JR; Sonsa-Ard, T; Teymourian, H; Wang, J, 2021)	0.62
" For significantly different metrics, their associations with clinical [levodopa equivalent daily dosage (LEDD), motor and visuospatial function] and SNc susceptibility MRI metrics [R2* and quantitative susceptibility mapping (QSM)] were explored."	( Choroidal Thickness Correlates with Clinical and Imaging Metrics of Parkinson's Disease: A Pilot Study. Bowie, EM; Brown, DA; Brown, GL; Camacci, ML; Du, G; Grillo, S; Huang, X; Kim, SD; Kong, L; Lewis, MM; Nguyen, JV; Sundstrom, JM; Ullah, SP, 2021)	0.85
"75]) taking one of three types of non-ergot extended-release DAs (rotigotine 32; pramipexole 44; ropinirole 36) with or without L-dopa (median daily total dosage of antiparkinsonian drugs 525."	( Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson's disease. Ando, H; Doyu, M; Fujikake, A; Fukuoka, T; Hayashi, M; Ito, C; Izumi, M; Kawagashira, Y; Koide, H; Nakashima, K; Niwa, JI; Ogawa, K; Oiwa, H; Okada, Y; Taguchi, S; Tokui, K; Tsunoda, Y; Yasumoto, A; Yuasa, T, 2021)	0.62
"For the whole PD patient cohort, the PDSS-2 sleep disturbance domain score and the scores for item 1 assessing sleep quality and item 8 assessing nocturia were positively correlated with daily total dosage of antiparkinsonian drugs and dosage of L-dopa, but not with the dosage of DAs."	( Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson's disease. Ando, H; Doyu, M; Fujikake, A; Fukuoka, T; Hayashi, M; Ito, C; Izumi, M; Kawagashira, Y; Koide, H; Nakashima, K; Niwa, JI; Ogawa, K; Oiwa, H; Okada, Y; Taguchi, S; Tokui, K; Tsunoda, Y; Yasumoto, A; Yuasa, T, 2021)	0.62
" Thus, adjusting both the total dosage of antiparkinsonian drugs and the dose-ratio of L-dopa might be key actions for alleviating poor sleep quality in patients with PD."	( Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson's disease. Ando, H; Doyu, M; Fujikake, A; Fukuoka, T; Hayashi, M; Ito, C; Izumi, M; Kawagashira, Y; Koide, H; Nakashima, K; Niwa, JI; Ogawa, K; Oiwa, H; Okada, Y; Taguchi, S; Tokui, K; Tsunoda, Y; Yasumoto, A; Yuasa, T, 2021)	0.62
"Long-term therapeutic efficacy of STN-DBS could be achieved even with relatively low stimulation intensity and medication dosage for PD patients in southern China."	( Eight-year follow-up outcome of subthalamic deep brain stimulation for Parkinson's disease: Maintenance of therapeutic efficacy with a relatively low levodopa dosage and stimulation intensity. Chen, J; Chen, L; Chen, W; Fu, X; Gu, J; Guo, Q; Hu, Y; Jiang, L; Liu, J; Liu, Y; Qian, H; Wu, L; Xian, W; Xu, S; Yang, C; Ye, J; Zheng, Y, 2021)	0.82
" Foslevodopa/foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups."	( Foslevodopa/Foscarbidopa Is Well Tolerated and Maintains Stable Levodopa and Carbidopa Exposure Following Subcutaneous Infusion. Facheris, MF; Liu, W; Neenan, M; Rosebraugh, M, 2021)	1.8
" Voluntary oral dosing compliance was recorded and quantified throughout the study."	( Voluntary oral dosing for precise experimental compound delivery in adult rats. Allen, RA; Bales, KL; Chesler, KC; Motz, CT; Pardue, MT; Vo, HK, 2022)	0.72
"BeyoND is an open-label study evaluating the long-term safety of two ND0612 dosing regimens."	( Subcutaneous Levodopa Infusion for Parkinson's Disease: 1-Year Data from the Open-Label BeyoND Study. Adar, L; Arkadir, D; Case, R; Ebersbach, G; Ellenbogen, AL; Espay, AJ; Fuchs Orenbach, S; Giladi, N; Isaacson, SH; Kieburtz, K; LeWitt, P; Olanow, CW; Oren, S; Poewe, W; Rosenfeld, O; Sasson, N; Simuni, T; Stocchi, F; Thomas, A; Yardeni, T; Zlotogorski, A, 2021)	0.99
" She was diagnosed with dyskinesia-hyperpyrexia syndrome (DHS) due to increasing dosage of ropinirole and infection."	( Rhabdomyolysis Associated with Severe Levodopa-Induced Dyskinesia in Parkinson's Disease: A Report of Two Cases and Literature Review. Pitakpatapee, Y; Sangpeamsook, T; Srikajon, J; Srivanitchapoom, P, 2021)	0.89
" We measured serum zinc levels and analyzed correlations between serum zinc levels, the levodopa oral administration period, dosage, dosing frequency, and zinc deficiency symptoms including taste disorders."	( Correlation between Serum Zinc Levels and Levodopa in Parkinson's Disease. Hirata, Y; Ishikawa, H; Kato, N; Matsuura, K; Matsuyama, H; Narita, Y; Niwa, A; Tomimoto, H, 2021)	1.11
"With the levodopa threshold effect for dyskinesia observed, threshold dosage of levodopa was identified in the general Parkinson's disease (PD) population."	( Effect of onset age on the levodopa threshold dosage for dyskinesia in Parkinson's disease. Chen, H; Feng, T; Kou, W; Liu, G; Ma, H; Su, D; Wang, D; Wang, X; Wang, Z; Zhang, Z; Zhao, J, 2022)	1.44
"EOPD patients had lower levodopa threshold dosage comparing with LOPD patients."	( Effect of onset age on the levodopa threshold dosage for dyskinesia in Parkinson's disease. Chen, H; Feng, T; Kou, W; Liu, G; Ma, H; Su, D; Wang, D; Wang, X; Wang, Z; Zhang, Z; Zhao, J, 2022)	1.33
" However prolonged administration and high dosing leads to the emergence of motor complications, which are involuntary movements, so called dyskinesia, and ‘OFF’ episodes."	( GOCOVRI Müller, T, 2022)	0.72
" No correlation was found between the ESS scores and Levodopa Equivalent Dosage (LED) or between the scores obtained from the sleep scales and the scores obtained from the UPDRS and BDI."	( Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients. Agan, K; Gunal, DI; Jafarova, S; Oner, OG; Seker, A; Sunter, G, 2022)	0.97
" The P2B001 combination has the potential to provide greater efficacy than either pramipexole or rasagiline alone and a better tolerability profile compared to higher dosage dopamine agonist monotherapy, while maintaining the advantage of lower motor complication risk than levodopa."	( P2B001 (Extended Release Pramipexole and Rasagiline): A New Treatment Option in Development for Parkinson's Disease. Brotchie, J; Friedman, H; Giladi, N; Hauser, RA; Litman, P; Oren, S; Poewe, W, 2022)	0.9
" The P2B001 combination has the potential to provide greater efficacy than either pramipexole or rasagiline alone and a better tolerability profile compared to higher dosage dopamine agonist monotherapy, while maintaining the advantage of lower motor complication risk than levodopa."	( P2B001 (Extended Release Pramipexole and Rasagiline): A New Treatment Option in Development for Parkinson's Disease. Brotchie, J; Friedman, H; Giladi, N; Hauser, RA; Litman, P; Oren, S; Poewe, W, 2022)	0.9
" Expression of both networks was significantly elevated in participants with PD relative to healthy volunteers and were not related to levodopa dosage or motor severity."	( Gait-Related Metabolic Covariance Networks at Rest in Parkinson's Disease. Alcock, L; Brooks, DJ; Burn, DJ; Colloby, SJ; Firbank, MJ; Galna, B; Lawson, RA; Lord, S; O'Brien, JT; Pavese, N; Rochester, L; Sigurdsson, HP; Taylor, JP; Yarnall, AJ, 2022)	0.92
" This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual's symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome."	( Identifying rates and risk factors for medication errors during hospitalization in the Australian Parkinson's disease population: A 3-year, multi-center study. Bakker, M; Corre, L; Johnson, JL; Johnson, ME; Li, X; Mill, DN; Woodman, RJ, 2022)	0.72
" This difficulty is a result of levodopa's short half-life, a progressive narrowing of the therapeutic window, and major inter-patient and intra-patient variations in the dose-response relationship."	( Closing the loop for patients with Parkinson disease: where are we? Kotagiri, YG; Litvan, I; Longardner, K; Mahato, K; Moon, JM; Podhajny, T; Sempionatto, JR; Tehrani, F; Teymourian, H; Wang, J, 2022)	1
" These include the timing, dosage and administration of levodopa, concomitant drugs, food, PD-associated non-motor symptoms, and various neurologic and non-neurologic comorbidities."	( Practical pearls to improve the efficacy and tolerability of levodopa in Parkinson's disease. Bahroo, L; Di Maria, G; Jankovic, J; Lamotte, G; Lenka, A, 2022)	1.21
" Carbidopa dosing is crucial as it not only enhances the entry of levodopa into the central nervous system but also reduces levodopa's peripheral adverse effects."	( Practical pearls to improve the efficacy and tolerability of levodopa in Parkinson's disease. Bahroo, L; Di Maria, G; Jankovic, J; Lamotte, G; Lenka, A, 2022)	1.2
" Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs."	( Parkinsonism-Hyperpyrexia Syndrome and Dyskinesia-Hyperpyrexia Syndrome in Parkinson's Disease: Two Cases and Literature Review. Hu, BL; Huang, JF; Huang, SS; Liu, RP; Wang, JY; Zhang, X; Zhu, JH; Zhu, SG, 2022)	0.72
"As of 2019, no impulsive control disorders, motor fluctuations, or DBS-related complications were observed during a 4-year follow-up, with 66% Unified Parkinson's Disease Rating Scale Part III reduction at medication OFF state noted, whereas levodopa equivalent daily dosage decreased by almost half."	( Long-term efficacy of bilateral subthalamic deep brain stimulation in the parkinsonism of SCA 3: A rare case report. Kuo, MC; Tai, CH; Tseng, SH; Wu, RM, 2022)	0.9
"01) in the second period, but with similar dosing frequency."	( Ten-year trends of the characteristics in patients with advanced Parkinson's disease at the time of intestinal gel therapy introduction Baróti, B; Constantin, V; Forró, T; Frigy, A; Kelemen, K; Metz, J; Mihály, I; Orbán-Kis, K; Szász, JA; Szász, RM; Szatmári, S; Török, Á, 2022)	0.72
"To evaluate the effects of once-daily opicapone on levodopa plasma pharmacokinetics and motor response when added to two different levodopa dosing regimens."	( Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease. Antonini, A; Ferreira, JJ; Guimarães, B; Moreira, J; Poewe, W; Rascol, O; Rocha, JF; Soares-da-Silva, P; Stocchi, F, 2022)	1.28
" To show that generic drugs are equivalent to the originator drug, regulations usually refer to the bioavailability of active ingredients, which is influenced by the selected dosage form and the chosen excipients."	( Different dissolution conditions affect stability and dissolution profiles of bioequivalent levodopa-containing oral dosage forms. Langer, K; Rose, O; Weitzel, J; Wünsch, A, 2022)	0.94
"Compared with TD subtype, patients with PIGD subtype have longer course of disease, higher disease severity, and higher daily dosage of levodopa."	( The Importance of Early Identification for Parkinson's Disease Patients with Postural Instability and Gait Disturbance. Gu, SC; Shi, R; Wang, CD; Wu, Y; Yang, YW; Ye, Q; Yuan, CX; Zhang, Y, 2022)	0.92
" The dosage of levodopa was 696."	( Use of Cen, L; Dongfang, C; Xianzhi, M; Zhongke, H, )	0.48
"609) and Levodopa dosage (P = 0."	( Data-driven subtyping of Parkinson's disease: comparison of current methodologies and application to the Bochum PNS cohort. Chen, Q; Gold, R; Mosig, A; Pitarokoili, K; Scherbaum, R; Tönges, L; Zella, S, 2023)	1.33
" Increasing dosing of levodopa weakens the methylation potential in the brain as a result of the methyl group consuming conversion of levodopa to 3-O-methyldopa in glial cells."	( The role of istradefylline in the Parkinson's disease armamentarium. Müller, T, 2023)	1.22
" Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS)."	( Comparison of dyskinesia profiles after L-DOPA dose challenges with or without dopamine agonist coadministration. Cenci, MA; Espa, E; Grigoriou, S; Jakobsson, A; Odin, P; Timpka, J; von Grothusen, G, 2023)	0.91
" Lower Levodopa Equivalent Dosage (LED) and calf circumference (CC) were independently associated with confirmed sarcopenia."	( Screening Tools for Sarcopenia in Mild to Moderate Parkinson's Disease: Assessing the Accuracy of SARC-F and Calf Circumference. Braga-Neto, P; Bruno, LB; Cunha, LCV; de Almeida, SB; de Luna, JRG; Feitosa, CX; Gomes, VC; Gradvohl, LB; Lima, DP; Lindsay Silva Marques, M; Marques da Silva, TA; Monteiro, PA; Montenegro-Júnior, RM; Roriz-Filho, JS; Viana-Júnior, AB, 2023)	1.37
" Such a formulation is expected to produce steady concentrations and prolong therapeutic duration compared to a common CRF with a smaller dose per day and a lower overall dose of levodopa, thereby improving patient compliance with the dosage regime."	( Model-based optimization of controlled release formulation of levodopa for Parkinson's disease. Arav, Y; Zohar, A, 2023)	1.34
" To study whether human equivalent doses of L-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral L-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length."	( Human equivalent doses of L-DOPA rescues retinal morphology and visual function in a murine model of albinism. Griffiths, H; Keeling, E; Lee, H; Lotery, AJ; Lynn, SA; Macdonald, SL; Newall, T; Ratnayaka, JA; Sanchez-Bretano, A; Scott, JA; Self, JE; Soundara-Pandi, SP, 2023)	0.91