phenytoin

Research Excerpts

Overview

Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is a prototypic drug prescribed for the treatment of a variety of seizure disorders. Its alkaline aqueous vehicle is associated with dermatologic irritation when rapidly infused.

Excerpt	Reference	Relevance
"Phenytoin is a relatively weaker substrate for each, and the drugs haloperidol, clozapine, and flunitrazepam are transported hardly or not at all."	( P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. Mol, CA; Schinkel, AH; van Deemter, L; Wagenaar, E, 1996)	1.02
"Phenytoin is a commonly used antiepileptic drug for various types of seizure disorders except for absent seizures. "	( 'Phenytoin: Shepherd or Wolf in Disguise? Phenytoin-Induced Neurotoxicity: A Case Series. Arora, M; Bhanwra, S; Boruah, DK; Thakker, V, )	2.48
"Phenytoin is a known human teratogen with unknown etiology. "	( The effect of phenytoin on embryonic heart rate in Vivo. Ababneh, D; Abela, D; Farrell, E; Hegedus, E; Howe, AM; Ritchie, HE, 2021)	2.42
"IV phenytoin is an established treatment of SE, but its alkaline aqueous vehicle is associated with dermatologic irritation and systemic complications when rapidly infused. "	( A critical review of fosphenytoin sodium injection for the treatment of status epilepticus in adults and children. Clay, JL; Fountain, NB, 2022)	1.65
"Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. "	( Acute exposure to environmentally relevant concentrations of phenytoin damages early development and induces oxidative stress in zebrafish embryos. Cardoso-Vera, JD; Elizalde-Velázquez, GA; Galar-Martínez, M; García-Medina, S; Gómez-Oliván, LM; Heredia-García, G; Islas-Flores, H; Orozco-Hernández, JM; SanJuan-Reyes, N, 2022)	2.41
"Phenytoin is a powerful antiseizure drug with complex pharmacokinetic properties, making it an interesting model drug to use in preclinical in vivo investigations, especially with regards to formulations aiming to improve drug delivery to the brain. "	( A sensitive LC-MS/MS method for quantification of phenytoin and its major metabolite with application to in vivo investigations of intravenous and intranasal phenytoin delivery. Prentice, RN; Rizwan, SB; Younus, M, 2022)	2.42
"Phenytoin is a prototypic drug prescribed for the treatment of a variety of seizure disorders."	( Cutaneous Hypersensitivity Reaction After Phenytoin Therapy in a Neonate: A Case Report and Review of Literature Elucidating the Potential Pharmacological Plausibility and Preventive Strategies. Prabath, I; Rajendran, P; Rani, J, 2023)	1.9
"Phenytoin is a versatile drug with utility in neurological, dermatological, and even cardiac disease processes. "	( Use of supra-therapeutic phenytoin for management of ventricular arrhythmias in children: Case series and literature review. Bhansali, S; Cecchin, F; Spilios, M; Tan, RBM, 2022)	2.47
"Phenytoin (PHT) is a first-line antiepileptic drug in clinics, which could decrease neuronal bioelectric activity by blocking the voltage-operated sodium channels. "	( Calcium Phosphate-Based Nanoformulation Selectively Abolishes Phenytoin Resistance in Epileptic Neurons for Ceasing Seizures. Cao, D; Guan, Q; Li, M; Luo, Z; Mao, X; Wang, X, 2023)	2.59
"Phenytoin (DFH), is an anticonvulsant widely used for the treatment of different types of seizures.(1) Therapeutic monitoring (TDM) is required for DFH due to its narrow therapeutic range and nonlinear pharmacokinetics, among other characteristics. "	( [Validation of the immunological method of kinetic interaction of microparticles in solution (KIMS) for the determination of phenytoin in saliva at the Hospital de Niños de Santísima Trinidad.] Ducheins, S; Gonzalez, II; Minetti, A; Rivolta, S; Suarez, HA, 2023)	2.56
"Phenytoin is an anticonvulsant drug which causes fibroblast proliferation, collagen synthesis, and an increase in epidermal growth factor. "	( Effects of phenytoin injection on vocal cord healing after mechanical trauma: An experimental study Akın, İ; Alicura Tokgöz, S; Beşaltı, Ö; Çadallı Tatar, E; Çalışkan, M; Kılıçaslan, S; Köybaşıoğlu, F; Saka, C, 2019)	2.35
"Phenytoin is a low solubility anticonvulsant drug. "	( Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization. Alves, G; Peixoto, D; Pires, PC; Rodrigues, M; Santos, AO; Teixeira, I, 2020)	2.25
"Phenytoin is a commonly used drug, and its metabolism is mediated by a specific cytochrome-P"	( Phenytoin intoxication associated with omeprazole administration in a child with defective CYP2C9. Agolini, E; Cecchetti, C; Cocciadiferro, D; Goffredo, BM; Marano, M; Nicoletti, F; Piervincenzi, E; Pro, S, 2020)	2.72
"Phenytoin is a hydantoin derivative that is used clinically for the treatment of epilepsy and has been reported to have antiarrhythmic actions on the heart. "	( Phenytoin Reduces Activity of Cardiac Ryanodine Receptor 2; A Potential Mechanism for Its Cardioprotective Action. Ashna, A; Dos Remedios, C; Laver, DR; Molenaar, P; van Helden, DF, 2020)	3.44
"Phenytoin (PHT) is a common causative drug for severe cutaneous adverse drug reactions (SCARs) in children. "	( Association of HLA genotypes with phenytoin induced severe cutaneous adverse drug reactions in Thai children. Benjaponpitak, S; Inunchot, W; Kamchaisatian, W; Khongkhatithuml, C; Likkasittipan, P; Mahasirimongkol, S; Manuyakorn, W; Suvichapanich, S; Thampratankul, L; Wattanapokayakit, S; Wichukchinda, N, 2020)	2.28
"Phenytoin is a long-standing, anti-seizure drug widely used in clinical practice. "	( Phenytoin - An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology. Kuca, K; Nepovimova, E; Patocka, J; Wu, Q, 2020)	3.44
"Phenytoin (PHT) is a routinely prescribed prophylactic antiepileptic following aneurysmal subarachnoid hemorrhage (aSAH). "	( Aneurysmal Subarachnoid Hemorrhage: Impact on Phenytoin Permeability across the Blood-Brain Barrier. Attri, SV; Dhir, N; Gill, NK; Kumar, MP; Mohindra, S; Patial, A; Pattanaik, S; Rathore, N; Saha, L, )	1.83
"Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. "	( Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Callaghan, JT; Caudle, KE; Fohner, AE; Formea, CM; Gaedigk, A; Huddart, R; Karnes, JH; Klein, TE; Llerena, A; Mintzer, S; Phillips, EJ; Rettie, AE; Somogyi, AA; Ta Michael Lee, M; Whirl-Carrillo, M, 2021)	2.28
"Phenytoin is an antiepileptic drug that is primarily eliminated by hepatic metabolism."	( Phenytoin Toxicity After Transjugular Intrahepatic Portosystemic Shunt (TIPS). Aminlari, A; Bassell, T; Del Rosso, J; Hayden, S; Ly, BT, 2021)	2.79
"Phenytoin is a low aqueous solubility antiepileptic drug, but its phosphate ester prodrug fosphenytoin is soluble, although less permeable. "	( Nose-to-brain delivery of phenytoin and its hydrophilic prodrug fosphenytoin combined in a microemulsion - formulation development and in vivo pharmacokinetics. Alves, G; Fazendeiro, AC; Pires, PC; Rodrigues, M; Santos, AO, 2021)	2.36
"Phenytoin is an 80-year young molecule and new indications are still emerging. "	( Phenytoin: neuroprotection or neurotoxicity? Keppel Hesselink, JM; Kopsky, DJ, 2017)	3.34
"Phenytoin is a widely used anticonvulsant, which is used in cutaneous medicine for treatment of ulcers and epidermolysis bullosa."	( Evaluation of the effect and mechanism of action of local phenytoin in treatment of vitiligo. Abdelwahed Gaber, M; Abdou, AG; Elnagar, A; Elnaidany, NF, 2017)	1.42
"Phenytoin (PHT) is an effective and inexpensive antiepileptic drug (AED). "	( Risk factors of early adverse drug reactions with phenytoin: A prospective inpatient cohort. Ciampi, E; Godoy, J; Mellado, P; Plaza, J; Uribe-San-Martín, R; Uslar, W; Villagra, S, 2017)	2.15
"Phenytoin is a widely used AED associated with easily detectable ADR through structured pharmacovigilance. "	( Risk factors of early adverse drug reactions with phenytoin: A prospective inpatient cohort. Ciampi, E; Godoy, J; Mellado, P; Plaza, J; Uribe-San-Martín, R; Uslar, W; Villagra, S, 2017)	2.15
"Phenytoin is an effective anticonvulsant for focal epilepsy. "	( Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics. Aeschlimann, DP; Aeschlimann, PC; Dennis, GJ; Grünewald, RA; Hadjivassiliou, M; Hoggard, N; Howell, SJ; Reuber, M; Shanmugarajah, PD, 2018)	3.37
"Phenytoin sodium (PS) is a narrow therapeutic index drug that dictates maintenance of narrow plasma concentration of the drug. "	( Effect of processing parameters and controlled environment storage on the disproportionation and dissolution of extended-release capsule of phenytoin sodium. Afrooz, H; Barakh Ali, SF; Dharani, S; Khan, MA; Rahman, Z; Reddy, IK, 2018)	2.13
"Phenytoin appears to be a promising drug that promotes periodontal regeneration."	( Topical application of phenytoin or nifedipine-loaded PLGA microspheres promotes periodontal regeneration in vivo. Bian, Z; Fang, YJ; Meng, LY; Tay, FR; Zhao, XH, 2019)	1.55
"Phenytoin is a major anticonvulsant drug that is effective to improve arrhythmia and neuropathic pain. "	( New mechanisms of phenytoin in calcium homeostasis: competitive inhibition of CD38 in hippocampal cells. Dehghan, G; Sadeghi, L; Yekta, R, 2018)	2.26
"Phenytoin is a non-sedative barbiturate derivate and has been recently rediscovered as a neuroprotective and retinoprotective compound in patients affected by optic neuritis secondary to multiple sclerosis. "	( The retinoprotective role of phenytoin. Bartollino, S; Chiosi, F; Costagliola, C; di Staso, S; Hesselink, JMK; Pascotto, A; Rinaldi, M; Uva, M, 2018)	2.21
"Phenytoin (Dilantin) is an orally active, use-dependent voltage-gated sodium channel inhibitor and is a potent, economical, and widely used anticonvulsant agent. "	( Naringin in a combined therapy with phenytoin on pentylenetetrazole-induced kindling in rats. Akula, A; Danduga, RCSR; Ineedi, S; Kola, PK; Mohammad, A; Nissankara Rao, LS, 2018)	2.2
"Phenytoin is an anticonvulsant which is also a Class IB antiarrhythmic. "	( Phenytoin-induced bradycardia and hypotension. Badyal, DK; Mathew, R; Mathews, SR, )	3.02
"Phenytoin is a strongly protein-bound anticonvulsant requiring free drug monitoring for certain patients. "	( PETINIA total phenytoin assay on the vista 1500 analyzer is not suitable for monitoring free phenytoin concentration if ultrafiltration is performed at room temperature. Dasgupta, A; Davis, B; Everett, JM, 2013)	2.19
"Phenytoin (DPH) is an anticonvulsant drug that is widely used for the treatment of epilepsy."	( A novel mouse model for phenytoin-induced liver injury: involvement of immune-related factors and P450-mediated metabolism. Fukami, T; Iida, A; Matsuo, K; Nakajima, M; Sasaki, E; Tsuneyama, K; Yokoi, T, 2013)	1.42
"Phenytoin is an antiepileptic drug that has been shown to reduce some neurotoxic effects of glutamate in states when glutamate neurotransmission is increased, such as neurodegeneration and stress. "	( Effect of phenytoin treatment on cell proliferation in the hippocampus and the heart and related neuroendocrine changes under non-stress and stress conditions. Babic, S; Jezova, D, 2014)	2.25
"Phenytoin is a widely used antiepileptic drug. "	( Mechanisms of phenytoin-induced toxicity in freshly isolated rat hepatocytes and the protective effects of taurine and/or melatonin. Eghbal, MA; Sattari, MR; Taziki, S, 2014)	2.21
"Phenytoin is an anticonvulsant that has been used in wound healing. "	( [Scientific production on the applicability of phenytoin in wound healing]. Alves, Gda S; de Almeida, AM; e Silva, Rde J; Firmino, F; Grandeiro, Dda S; Penna, LH, 2014)	2.1
"Phenytoin is a commonly used anticonvulsant that is highly protein bound with a narrow therapeutic range. "	( An automated real-time free phenytoin assay to replace the obsolete Abbott TDx method. Akl, P; Blick, K; Jones, R; Williams, C, 2014)	2.14
"Phenytoin is an effective anti-epileptic drug that inhibits Na(+) channel activities; however, how phenytoin modulates synaptic transmission to soothe epileptic symptoms is not clear. "	( Phenytoin attenuates the hyper-exciting neurotransmission in cultured embryonic cortical neurons. Chou, MY; Lee, CY; Liou, HH; Pan, CY, 2014)	3.29
"Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). "	( Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Callaghan, JT; Caudle, KE; Klein, TE; Lee, MT; Mintzer, S; Rettie, AE; Smith, LH; Whirl-Carrillo, M, 2014)	2.06
"Phenytoin (PHT) is a commonly prescribed first-line antiepileptic drug. "	( Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice. He, Y; Li, W; Lin, Y; Weng, W; Xu, H; Yang, H; Zhang, S; Zheng, H; Zhou, Z; Zhu, L, 2015)	2.09
"Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. "	( Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation. Campos-Ordonez, T; Galvez-Contreras, AY; Gonzalez-Castaneda, RE; Gonzalez-Perez, O; Luquin, S, 2016)	3.32
"Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. "	( Cardiovascular adverse effects of phenytoin. Guldiken, B; Noachtar, S; Rémi, J, 2016)	2.16
"Phenytoin is a common medication for seizure treatment and prophylaxis in the intensive care unit (ICU). "	( Correlation of Free and Total Phenytoin Serum Concentrations in Critically Ill Patients. Barletta, JF; Bikin, DS; Buckley, MS; Reeves, BA, 2016)	2.17
"Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). "	( Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population. Chang, CC; Choon, SE; Chung, WH; Hussein, SH; Lee, CK; Lim, KS; Murad, S; Ng, CC; Too, CL, 2017)	2.15
"Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. "	( Anti-epileptic drugs and bone loss: Phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells. Fuller, HR; Garton, M; Wilson, EL, 2016)	2.15
"Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain-of-function mutations of SCN8A."	( The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin. Barker, BS; Hollander, RM; Meisler, MH; Ottolini, M; Patel, MK; Wagnon, JL, 2016)	1.37
"Phenytoin is a drug which could stimulate fibroblasts to produce collagen."	( Phenytoin accelerates tendon healing in a rat model of Achilles tendon rupture. Akbari, MG; Ghabili, M; Hajipour, B; Kermani, TA; Laleh, FM; Miyandoab, TM; Mohammad, SA; Mousavi, G; Navali, AM; Roshangar, L; Saleh, BM, 2016)	2.6
"Phenytoin is a commonly used antiepileptic medication in the pediatric age group, but it has a narrow therapeutic range. "	( Phenytoin-induced encephalopathy in a child. Mehndiratta, S, )	3.02
"Phenytoin is a drug more commonly used in the treatment of epilepsy, but may play an important role in accelerating ulcer healing."	( Topical phenytoin for treating pressure ulcers. Cai, H; Guo, TK; Hao, XY; Jiang, L; Li, HL; Liu, R; Shen, YF; Su, H, 2017)	1.61
"Phenytoin is a widely used anticonvulsant agent responsible for a number of intentional and unintentional overdoses. "	( Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion. Eyer, F; Felgenhauer, N; Pfab, R; Thürmel, K; Zilker, T, 2008)	2.07
"Phenytoin is a widely used anti-seizure agent, and a good correlation is observed between its concentration in plasma and the clinical effect. "	( Determination of free and total levels of phenytoin in human plasma from patients with epilepsy by MEKC: an adequate alternative to HPLC. Chen, SH; Hsieh, YH; Liao, FF; Lin, PC, 2010)	2.07
"Phenytoin (PHT) is a risk factor of cleft palate formation; however, the molecular mechanisms by which phenytoin exerts its teratogenic effects resulting in cleft palate remain unknown."	( Effects of phenytoin on Satb2 and Hoxa2 gene expressions in mouse embryonic craniofacial tissue. Mao, XY; Tang, SJ, 2010)	1.47
"Oral phenytoin is an extensively used medicine for the treatment of convulsive disorders. "	( Two percent topical phenytoin sodium solution in treating pyoderma gangrenosum: a cohort study. Dissanayake, M; Ekanayake, SM; Fonseka, HF, 2010)	1.2
"Phenytoin is a low cost drug, which accelerates skin wounds healing in human patients."	( Assessment of the effect of phenytoin on cutaneous healing from excision of melanocytic nevi on the face and on the back. Alchorne, Ade O; Pereira, CA, 2010)	1.38
"Phenytoin is an anti-convulsant and anti-arrhythmic medication. "	( Phenytoin (Dilantin) and acupuncture therapy in the treatment of intractable oral and facial pain. Lu, DP; Lu, GP; Lu, WI, 2011)	3.25
"Phenytoin is an established antiepileptic drug that has been used occasionally to treat intractable trigeminal neuralgia."	( Phenytoin for neuropathic pain and fibromyalgia in adults. Birse, F; Derry, S; Moore, RA, 2012)	2.54
"Phenytoin is an inductor of the main metabolizing enzyme of ivabradine and it could influence its pharmacokinetics. "	( Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects. Leucuta, SE; Muntean, D; Neag, M; Popa, A; Vlase, L, 2012)	2.07
"Phenytoin is a commonly prescribed anticonvulsant drug; however, there is evidence that long-term administration is related to cerebellar ataxia, cerebellar atrophy, loss of Purkinje cells, and hyperplasia of Bergman glia cells. "	( Dendritic, axonal, and spinal pathology of the Purkinje cells and the neurons of the dentate nucleus after long-term phenytoin administration: a case report. Baloyannis, SJ; Costa, VG; Kiourexidou, M; Manani, MG; Mavroudis, IA; Njau, SN; Petrides, F, 2013)	2.04
"Phenytoin is a well-characterized sodium channel blocker in widespread use as an anticonvulsant. "	( Phenytoin blocks retinal ganglion cell death after partial optic nerve crush. Naskar, R; Quinto, K; Romann, I; Schuettauf, F; Zurakowski, D, 2002)	3.2
"Fosphenytoin is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. "	( Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. Fischer, JH; Fischer, PA; Patel, TV, 2003)	1.56
"Phenytoin is a highly effective and widely prescribed anticonvulsant agent, but it can be associated with dose-related side effects and hypersensitivity reactions. "	( Phenytoin-induced toxic cholestatic hepatitis in a patient with skin lesions: case report. Altuntaş, Y; Erdem, L; Günes, G; Karul, S; Oztürk, B; Sengül, A; Uçak, S, 2003)	3.2
"Phenytoin is a known inducer of drugs metabolized by CYP2C, CYP2D, and CYP3A, but its own metabolism may be altered by drugs influencing CYP2C9 or CYP2C19, such as diazepam. "	( Phenytoin-diazepam interaction. Murphy, A; Wilbur, K, 2003)	3.2
"Phenytoin (PHT) is a first-line drug in the treatment of status epilepticus. "	( A comparison of central brain (cerebrospinal and extracellular fluids) and peripheral blood kinetics of phenytoin after intravenous phenytoin and fosphenytoin. Patsalos, PN; Wang, X, 2003)	1.98
"Phenytoin is a cheap and easy-to-use medicament, effective in suppressing burn wound bacteria and relieving pain thereby promoting healing, and may be advocated for the purpose in resource-scarce environments."	( A comparison of topical Phenytoin with Silverex in the treatment of superficial dermal burn wounds. Carneiro, PM; Mkony, CA; Rwanyuma, LR, )	1.88
"Phenytoin is an inducer of CYP3A4 activity, and a substrate and inducer of CYP2C9 and CYP2C19."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	1.31
"Phenytoin is an effective anticonvulsant that has not previously been studied prophylactically in bipolar (BP) patients. "	( Prophylactic effect of phenytoin in bipolar disorder: a controlled study. Bersudsky, Y; Mishory, A; Winokur, M, 2003)	2.07
"Phenytoin (PHT) is an antiepileptic drug known to have teratogenic effects. "	( Effect of prenatal phenytoin administration on the fine structure of rat myocardium and aorta. Dubovický, M; Guller, L; Mach, M; Okruhlicová, L; Sotníková, R; Tribulová, N; Ujházy, E, 2003)	2.09
"Phenytoin is an anticonvulsant drug known to interact with many other drugs. "	( Studying long-term effect of phenytoin either alone or combined with ascorbic acid on the anesthetic effect of urethane in rats. Abdulla, MM; El Desoky, ES, 2004)	2.06
"Phenytoin (PHT) is a CYP3A4 inducer and CYP2C9/CYP2C19 substrate."	( Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. Bertz, RJ; Eron, JJ; Gaedigk, A; Kashuba, AD; Lim, ML; Min, SS; Robinson, M, 2004)	1.31
"Phenytoin is an anticonvulsant used in the treatment of epilepsy. "	( Treatment of posttraumatic stress disorder with phenytoin: an open-label pilot study. Douglas Bremner, J; Heim, CM; Mletzko, T; Nemeroff, CB; Reed, L; Siddiq, S; Welter, S; Williams, C, 2004)	2.02
"Phenytoin is a commonly prescribed antiepileptic drug. "	( Acute phenytoin intoxication: causes, symptoms, misdiagnoses, and outcomes. Hwang, WJ; Tsai, JJ, 2004)	2.25
"Phenytoin is a widely used anticonvulsant that affects carbohydrate metabolism."	( The effects of phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin on cellular glucose transport. Chan, YW; Chu, TS; Fok, TF; Fung, KP; Fung, LW; Ho, YY; Wong, HY, 2005)	1.4
"Phenytoin (Dilantin) is an anticonvulsant used in the treatment of epilepsy. "	( Effects of phenytoin on memory, cognition and brain structure in post-traumatic stress disorder: a pilot study. Bremner, JD; Brummer, M; Heim, CM; Mletzko, T; Nemeroff, CB; Quinn, S; Reed, L; Siddiq, S; Welter, S; Williams, C, 2005)	2.16
"Phenytoin is an anticonvulsant that requires therapeutic drug monitoring. "	( Analytic performance evaluation of a new turbidimetric immunoassay for phenytoin on the ADVIA 1650 analyzer: effect of phenytoin metabolite and analogue. Dasgupta, A; Datta, P; Scurlock, D, 2005)	2
"Phenytoin is an antiepileptic drug that induces hepatic enzymes, affecting the cytochrome P450 3A family."	( Altered cytochrome p450 metabolism of calcineurin inhibitors: case report and review of the literature. Evans, CG; Formea, CM; Karlix, JL, 2005)	1.05
"Phenytoin appears to be an effective method for enhancing the take of the full-thickness skin graft. "	( Topical phenytoin ointment increases autograft acceptance in rats. Albsoul-Younes, A; Badran, DH; Younes, NA, 2006)	2.21
"Phenytoin is an anti-convulsant drug commonly used to prevent seizures in patients with cerebral metastases. "	( A case of phenytoin toxicity in a patient with advanced lung cancer. Jenkins, A, 2006)	2.18
"Phenytoin is a human and animal teratogen. "	( Increased susceptibility to phenytoin teratogenicity: excessive generation of reactive oxygen species or impaired antioxidant defense? Azarbayjani, F; Borg, LA; Danielsson, BR, 2006)	2.07
"As phenytoin is a commonly used drug, clinicians need to be aware of this interaction."	( Is phenytoin administration safe in a hypothermic child? Arora, R; Bhagat, H; Bithal, PK; Chouhan, RS, 2006)	1.47
"Phenytoin (DPH) is a clinically useful sodium (Na) channel blocker with efficacy against partial and generalized seizures. "	( A pharmacophore derived phenytoin analogue with increased affinity for slow inactivated sodium channels exhibits a desired anticonvulsant profile. Batts, TW; Brown, ML; Davis, GC; Hartmann, HA; Jones, PJ; Ko, SH; Lenkowski, PW; McCusker, AK; Patel, MK; Smith, MD; Taylor, CH; White, HS, 2007)	2.09
"Phenytoin solution is a safe topical agent that accelerates healing of pressure ulcers. "	( Topical phenytoin solution for treating pressure ulcers: a prospective, randomized, double-blind clinical trial. Chandy, SJ; Durai, S; George, J; Margaret Shanti, FX; Mathew, BS; Neelakantan, N; Subbanna, PK; Suresh, R; Tharion, G, 2007)	2.22
"Phenytoin is a first-line drug for the treatment of status epilepticus. "	( Phenytoin intoxication in a clozapine-related prolonged seizure. Gandelman-Marton, R; Klein, C; Rabey, JM; Theitler, J, 2008)	3.23
"Phenytoin is a drug used for the treatment of different types of seizures. "	( Undetectable phenytoin serum levels by an automated particle-enhanced turbidimetric inhibition immunoassay in a patient with monoclonal IgM lambda. Brauchli, YB; Krähenbühl, S; Scholer, A; Schwietert, M, 2008)	2.16
"Phenytoin is an alternate ligand for the glucocorticoid receptor affecting prostaglandin and/or thromboxane production."	( Biochemical mechanism of glucocorticoid-and phenytoin-induced cleft palate. Goldman, AS, 1984)	1.25
"Phenytoin continues to be a very popular drug for most types of seizures, but carbamazepine, used adjunctively until recently, is effective as monotherapy for the control of partial seizures, particularly those of the complex partial variety."	( Treatment of the nonconvulsive epilepsies. Dreifuss, FE, 1983)	0.99
"Phenytoin is a high-melting, weakly acidic, and sparingly water-soluble drug. "	( Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs. Roberts, RD; Stella, VJ; Yamaoka, Y, 1983)	2.09
"Phenytoin is a highly effective anticonvulsant medication that is considered to be the treatment of choice for generalized major motor and focal epileptic seizures. "	( Phenytoin: pharmacokinetics and clinical therapeutics. Finn, AL; Olanow, CW, 1981)	3.15
"Phenytoin is a logical drug for the treatment of severe tricyclic antidepressant poisoning signalled by first degree AV block and/or intraventricular conduction delay."	( Reversal of tricyclic-antidepressant-induced cardiac conduction abnormalities by phenytoin. Hagerman, GA; Hanashiro, PK, 1981)	1.21
"Phenytoin is a drug of considerable medical use, but very little is known about the various possible intermediate steps involved in its action."	( Phenytoin administration to pregnant mice: a mutagenic action? Ehrensperger, M; Lombard, MN; Petter, C, 1981)	2.43
"Phenytoin (DPH) is a widely used anticonvulsant drug but a conclusive mode of action is not yet clear. "	( Effect of chronic administration of phenytoin on regional monoamine levels in rat brain. Lakshmana, KM; Meshkibaf, MH; Rao, BS; Subhash, MN, 1995)	2.01
"Phenytoin therapy is a well recognized cause of gingival hyperplasia, a condition characterized by increased gingival collagen synthesis, and may also cause acromegalic-like facial features. "	( Phenytoin increases markers of osteogenesis for the human species in vitro and in vivo. Barr, B; Baylink, DJ; Houchin, K; Lau, KH; Nakade, O; Taylor, AK, 1995)	3.18
"Phenytoin is a lipophilic substance."	( [The influence of hyperlipidemia on pharmacokinetics of free phenytoin]. Dutkiewicz, G; Gawrońska-Szklarz, B; Wójcicki, J, )	1.09
"Phenytoin is a lipophilic substance."	( [The effect of hyperlipidemia on pharmacokinetics of free phenytoin]. Dudkiewicz, G; Gawrońska-Szklarz, B; Wójcik, J, )	1.1
"Phenytoin is an effective motion sickness countermeasure that may exert its effect through a combination of central nervous system and peripheral vestibular effects."	( Phenytoin for motion sickness: clinical evaluation. Chelen, W; Ferguson, R; Johnson, L; Knox, GW; Woodard, D, 1994)	2.45
"Phenytoin is a medication administered for the treatment or prophylaxis of seizures in head-injured patients. "	( Case study of two methods for enteral phenytoin administration. Bader, MK, 1993)	2
"Phenytoin is a potent inducer of carbamazepine metabolism. "	( Unmasking the significant enzyme-inducing effects of phenytoin on serum carbamazepine concentrations during phenytoin withdrawal. Abou-Elkair, M; Chapron, DJ; LaPierre, BA, 1993)	1.98
"Phenytoin appears to be an effective, low-cost and safe method for the treatment of partial-thickness skin graft donor sites, comparing very favourably with, and in some aspects superior to, occlusive dressings."	( Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing. Garg, S; Kumar, N; Singhvi, AM; Yadav, JK, 1993)	1.44
"Phenytoin (PHT) is a commonly used anticonvulsant drug; several side effects have been described, including morphological changes in brain cortex and cerebellar neurons and teratogenic lesions in infants of epileptic mothers. "	( Influence of phenytoin on cytoskeletal organization and cell viability of immortalized mouse hippocampal neurons. Bahn, S; Bauer, J; Ganter, U; Otten, U; Volk, B, 1993)	2.1
"Phenytoin appears to be a useful agent for the promotion of healing of trophic leprosy ulcers."	( Comparison of topical phenytoin with normal saline in the treatment of chronic trophic ulcers in leprosy. Bansal, NK, 1993)	1.32
"Phenytoin is an effective operational countermeasure for motion sickness for selected SRB crewmembers."	( Phenytoin as a countermeasure for motion sickness in NASA maritime operations. Chelen, W; Ferguson, B; Knox, G; Myers, KJ; Woodard, D, 1993)	2.45
"Fosphenytoin is a water-soluble disodium phosphate ester of phenytoin that is converted in plasma to phenytoin. "	( Intravenous administration of fosphenytoin: options for the management of seizures. DeToledo, J; Ramsay, RE, 1996)	1.2
"Fosphenytoin is a new phenytoin prodrug that fulfills many of the properties of an ideal anticonvulsant drug."	( Intramuscular use of fosphenytoin: an overview. Ramsay, RE; Uthman, BM; Wilder, BJ, 1996)	1.11
"Phenytoin is a hydantoin-type anticonvulsive agent used extensively for nearly sixty years in the prophylactic treatment of grand mal and psychomotor seizures. "	( Perspective on the carcinogenic potential of phenytoin based on rodent tumor bioassays and human epidemiological data. de la Iglesia, FA; Dethloff, LA; Goldenthal, E; Gough, A; Graziano, MJ, 1996)	2
"Fosphenytoin is a phenytoin prodrug that received an approvable letter from the Food and Drug Administration in February 1996. "	( Fosphenytoin: a novel phenytoin prodrug. Boucher, BA, )	1.37
"Phenytoin is a widely used anticonvulsant which has a relatively narrow therapeutic range of serum concentrations, 40-80 mmol/l (10-20 mg/l). "	( Hypothyroxinemia and phenytoin toxicity: a vicious circle. Sarich, TC; Wright, JM, 1996)	2.06
"Phenytoin (pht) is an anticonvulsant drug commonly used for the prevention of seizures. "	( Phenytoin and cyclosporine A specifically regulate macrophage phenotype and expression of platelet-derived growth factor and interleukin-1 in vitro and in vivo: possible molecular mechanism of drug-induced gingival hyperplasia. Cutler, CW; Dill, RE; Doxey, D; Fojt, J; Gonzales, A; Iacopino, AM; Nares, S; Stoever, K, 1997)	3.18
"Fosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement for standard injectable sodium phenytoin. "	( Fosphenytoin (Cerebyx). Browne, TR, 1997)	1.54
"Phenytoin is a commonly used anticonvulsant drug for the prevention of seizures. "	( Myofibroblasts in phenytoin-induced hyperplastic connective tissue in the rat and in human gingival overgrowth. Dill, RE; Iacopino, AM, 1997)	2.07
"Phenytoin is a major antiepileptic drug for treatment of limbic seizures. "	( Phenytoin's effect on the spread of seizure activity in the amygdala kindling model. Cramer, S; Ebert, U; Löscher, W, 1997)	3.18
"Fosphenytoin (Cerebyx), is a water soluble prodrug that is rapidly and completely converted to phenytoin. "	( Intramuscular fosphenytoin (Cerebyx) in patients requiring a loading dose of phenytoin. Barkley, GL; Garnett, WR; Knapp, LE; Leppik, IE; Pellock, JM; Ramsay, RE; Uthman, BM; Wilder, BJ, 1997)	1.26
"Fosphenytoin is a parenteral prodrug of phenytoin that is more tolerable than parenteral phenytoin."	( Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin. Curry, WJ; Kulling, DL, 1998)	1.04
"Fosphenytoin is a phenytoin prodrug that has been introduced to overcome some of the problems and limitations associated with parenteral phenytoin sodium administration. "	( Fosphenytoin. Luer, MS, 1998)	1.54
"Phenytoin is a commonly used anti-epileptic drug. "	( Early-onset phenytoin toxicity mimicking a renopulmonary syndrome. Polman, AJ; Tiebosch, AT; van der Werf, TS; Zijlstra, JG, 1998)	2.12
"Fosphenytoin is a new phosphate ester prodrug of phenytoin. "	( Elevated free fosphenytoin concentrations in uremic sera: uremic toxins hippuric acid and indoxyl sulfate do not account for the impaired protein binding of fosphenytoin. Dasgupta, A; Havlik, D, 1998)	1.26
"Phenytoin (PHT) is a commonly used anticonvulsant drug. "	( Neurotoxic effects of phenytoin on postnatal mouse brain development following neonatal administration. Hatta, T; Murakami, T; Ohmori, H; Takano, M; Yamashita, K; Yasuda, M, )	1.89
"Phenytoin (PHT) is a primary antiepileptic drug. "	( Developmental neurotoxicity of phenytoin on granule cells and Purkinje cells in mouse cerebellum. Hatta, T; Kawano, K; Michikawa, T; Mikoshiba, K; Nakamura, S; Ogura, H; Ohmori, H; Yamashita, K; Yasuda, M, 1999)	2.03
"Phenytoin is a highly effective and widely prescribed anticonvulsant agent. "	( Anticonvulsant hypersensitivity syndrome occurring as sepsis with multiorgan dysfunction. Marik, P, 1999)	1.75
"Phenytoin (PHT) is a widely prescribed antiepileptic drug. "	( Genotoxicity of the anticonvulsant drug phenytoin (PHT): a follow-up study of PHT-untreated epileptic patients. I. Sister chromatid exchange (SCE) analysis. Goyle, S; Kaul, A, 1999)	2.01
"Fosphenytoin is a parenterally administered prodrug of phenytoin, used in the treatment of patients with seizures."	( Fosphenytoin. Pharmacoeconomic implications of therapy. Benfield, P; Holliday, SM; Plosker, GL, 1998)	1.44
"Phenytoin is an effective antiepileptic drug, although, it can be associated with many side effects, including dyskinesia."	( Dyskinesia induced by phenytoin. Cendes, F; Montenegro, MA; Scotoni, AE, 1999)	2.06
"Phenytoin toxicity is an uncommon problem seen in clinical practice. "	( Paradoxical seizures in phenytoin toxicity. Chua, HC; Tan, CB; Tjia, H; Venketasubramanian, N, 1999)	2.05
"Phenytoin continues to be a preferred drug for treating generalised tonic-clonic seizures in the elderly and simple partial seizures that generalise."	( Differential kinetics of phenytoin in elderly patients. Bachmann, KA; Belloto, RJ, 1999)	1.33
"Phenytoin is a widely used anticonvulsant drug that also reduces aggressive behavior. "	( Phenytoin inhibits isolation-induced aggression specifically in rats with low serotonin. Keele, NB, 2001)	3.2
"Fosphenytoin is a phosphate ester prodrug of phenytoin that is significantly better tolerated parenterally than phenytoin in the treatment of epilepsy."	( Fosphenytoin: an intravenous option for the management of acute trigeminal neuralgia crisis. Cheshire, WP, 2001)	1.45
"Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. "	( How high can we go with phenytoin? Kobayashi, J; Koren, G; Kozer, E; Minassian, BA; Parvez, S; Verjee, Z, 2002)	2.06
"Fosphenytoin is a prodrug that is metabolized by phosphatases to yield the antiepileptic drug phenytoin plus inorganic phosphate. "	( Hypocalcemia-like electrocardiographic changes after administration of intravenous fosphenytoin. Blackshear, JL; Bondy, LR; Keegan, MT; Lanier, WL, 2002)	1.16
"Phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. "	( Clinical pharmacokinetics of phenytoin. Richens, A, )	1.87
"Phenytoin elimination is a saturable process obeying Michaelis-Menten kinetics. "	( Phenytoin intoxication during concurrent diazepam therapy. Haslam, RA; Lietman, PS; Longstreth, J; Rogers, HJ, 1977)	3.14
"Phenytoin is a central anticholinergic agent and a central stimulant of serotonin, and may induce movement disorders as a result of altering these neurotransmitters in the brain."	( Phenytoin-induced dystonia and choreoathetosis in two retarded epileptic children. Chalhub, EG; Devivo, DC; Volpe, JJ, 1976)	2.42
"Phenytoin is a well-tolerated alternative to magnesium sulfate for seizure prophylaxis in the patient with mild pregnancy-induced hypertension."	( Magnesium sulfate versus phenytoin for seizure prophylaxis in pregnancy-induced hypertension. Adams, HR; Appleton, MP; Gold, WR; Knight, AB; Kuehl, TJ; Raebel, MA, 1991)	1.31
"The phenytoin cells appear to be a unique phenotype."	( Effect of cell donor age on the synthetic properties of fibroblasts obtained from phenytoin-induced gingival hyperplasia. Johnson, BD; Narayanan, AS; Page, RC; Pieters, HP, 1990)	0.99
"Phenytoin (PHT) is a commonly used drug in children and adults, but it is often difficult to adjust the dosage to attain therapeutic drug concentrations due to the nonlinear nature of PHT metabolism. "	( Phenytoin dosage adjustment method using population clearance. Aoyama, T; Higuchi, S; Yukawa, E, 1990)	3.16
"Phenytoin is a major anticonvulsant drug that is very effective in controlling a wide variety of seizure disorders while impairing neurological function little, if at all. "	( Phenytoin: mechanisms of its anticonvulsant action. Pincus, JH; Selzer, ME; Yaari, Y, 1986)	3.16
"Phenytoin is a relatively safe medication even in the toxic range as determined by baseline phenytoin levels."	( Phenytoin toxicity: a review of 94 cases. Curtis, DL; Ellenhorn, MJ; Ordog, G; Piibe, R; Wasserberger, J, 1989)	2.44
"Phenytoin is a well tolerated drug whose efficacy appears similar to most standard antiarrhythmic agents."	( Efficacy of phenytoin in suppressing inducible ventricular tachyarrhythmias. Elson, JJ; Fiedler, SB; Fogoros, RN, 1988)	1.38
"Phenytoin is an established therapy for post-herpetic neuralgia. "	( Phenytoin monitoring: clinical or scientific? Carlile, AK; Fulton, JD; McCarron, BN; McGovern, EM, 1988)	3.16
"Phenytoin is a highly effective anticonvulsant agent that is widely administrated to prevent some kinds of patients with brain tumor. "	( [Effects of phenytoin on cell-mediated immunity]. Matsui, Y; Miyao, Y; Mogami, H; Okamoto, Y; Shimizu, K; Tamura, K; Tsuda, N; Yamada, M, 1987)	2.09
"Phenytoin is an alternate ligand for the glucocorticoid receptor affecting prostaglandin and/or thromboxane production."	( Palatal development and the arachidonic acid cascade. Goldman, AS; Piddington, RL, 1985)	0.99

Effects

Phenytoin sodium (PS) has a tendency to convert to its base form; phenytoin base (PHT) during manufacturing, packaging, shelf life and in-use conditions that can influence its clinical performance. PhenyToin has a wide range of pharmacologic effects other than its anticonvulsant activity.

Phenytoin has been shown to cause choreiform movements, peripheral neuropathy, and cognitive decline in some patients. It has marked enzyme-inducing properties and can stimulate the metabolism of many concurrently administered drugs, thereby reducing their therapeutic efficacy.

Excerpt	Reference	Relevance
"Phenytoin has an increased risk of toxicity given its narrow therapeutic window and variations in drug elimination."	( Cardiac Collapse Secondary to Phenytoin Toxicity in a Neonate Treated with Extracorporeal Membrane Oxygenation Support (ECMO). Barkemeyer, B; Brumund, M; Gupta, R; Knecht, M; LaRochelle, J; Mumphrey, C, 2020)	1.57
"Phenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. "	( A Novel Correction Equation Avoids High-Magnitude Errors in Interpreting Therapeutic Drug Monitoring of Phenytoin Among Critically Ill Patients. Barra, ME; Chung, DY; Phillips, KM; Rosenthal, ES, 2020)	2.22
"Phenytoin sodium (PS) has a tendency to convert to its base form; phenytoin base (PHT) during manufacturing, packaging, shelf life and in-use conditions that can influence its clinical performance. "	( Quantitative estimation of phenytoin sodium disproportionation in the formulations using vibration spectroscopies and multivariate methodologies. Afrooz, H; Barakh Ali, SF; Dharani, S; Khan, MA; Rahman, Z, 2018)	2.22
"Phenytoin has a narrow therapeutic window, and when managing cases of toxicity, clinicians are very wary of this fact. "	( Free phenytoin toxicity. Gambhir, H; Imam, SH; John, D; Kaul, V; Kloss, B; Landry, K, 2014)	2.36
"Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). "	( The effect of polymorphic metabolism enzymes on serum phenytoin level. Ergeç, D; Gulcebi, MI; Guney, I; Onat, FY; Ozkara, C; Ozkaynakci, A; Ulucan, K; Uzan, M, 2015)	2.11
"Phenytoin has a narrow therapeutic window and seizures can occur at both ends of the spectrum."	( Paradoxical Seizure Response to Phenytoin in an Epileptic Heroin Addict. Dewberry, RG; Pula, T; Vasagar, B; Verma, BR, 2015)	2.14
"Phenytoin has a narrow therapeutic range and exhibits concentration-dependent kinetics within this therapeutic window. "	( Elevated thyroid-stimulating hormone in a 65-year-old patient with phenytoin toxicity. Collins, RJ, 2008)	2.02
"Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. "	( Phenytoin revisited. Finkel, MJ, 1984)	3.15
"Phenytoin has a beneficial effect on wound healing and on the healing of bone fractures, while beta-aminopropionitrile (BAPN) has an adverse effect on both. "	( Effect of phenytoin and/or beta-aminoproprionitrile on a surgically induced periosteal wound. Kuebel, MA; Taylor, JJ; Yeager, VL, 1985)	2.11
"Phenytoin has the ability of promoting the differentiation of hDPSC into odontoblasts and osteoblasts. "	( Phenytoin Is Promoting the Differentiation of Dental Pulp Stem Cells into the Direction of Odontogenesis/Osteogenesis by Activating BMP4/Smad Pathway. Shang, W; Xiong, S, 2022)	3.61
"Phenytoin has well-studied sodium-channel blocking abilities which can be taken advantage of to treat ventricular arrhythmias."	( Use of supra-therapeutic phenytoin for management of ventricular arrhythmias in children: Case series and literature review. Bhansali, S; Cecchin, F; Spilios, M; Tan, RBM, 2022)	1.75
"Phenytoin has an increased risk of toxicity given its narrow therapeutic window and variations in drug elimination."	( Cardiac Collapse Secondary to Phenytoin Toxicity in a Neonate Treated with Extracorporeal Membrane Oxygenation Support (ECMO). Barkemeyer, B; Brumund, M; Gupta, R; Knecht, M; LaRochelle, J; Mumphrey, C, 2020)	1.57
"Phenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. "	( A Novel Correction Equation Avoids High-Magnitude Errors in Interpreting Therapeutic Drug Monitoring of Phenytoin Among Critically Ill Patients. Barra, ME; Chung, DY; Phillips, KM; Rosenthal, ES, 2020)	2.22
"Phenytoin has been shown to reduce the peripapillary retinal nerve fiber layer (pRNFL) loss in optic neuritis (ON). "	( Effect of phenytoin on retinal ganglion cells in acute isolated optic neuritis. Aghsaei Fard, M; Ghahvehchian, H; Gholizade, A; Yadegari, S, 2020)	2.4
"Phenytoin has traditionally been considered the second-line drug of first choice after failure of first-line treatment using benzodiazepines."	( Comparison of the efficacy and safety of levetiracetam and phenytoin in the treatment of established status epilepticus: A systematic review and meta-analysis. Cui, XH; Dong, XZ; Liu, JM; Liu, WN; Yang, L; Zhang, L, 2021)	1.59
"Phenytoin sodium (PS) has a tendency to convert to its base form; phenytoin base (PHT) during manufacturing, packaging, shelf life and in-use conditions that can influence its clinical performance. "	( Quantitative estimation of phenytoin sodium disproportionation in the formulations using vibration spectroscopies and multivariate methodologies. Afrooz, H; Barakh Ali, SF; Dharani, S; Khan, MA; Rahman, Z, 2018)	2.22
"Phenytoin has very challenging pharmacokinetic properties. "	( Therapeutic Drug Monitoring of Phenytoin by Simple, Rapid, Accurate, Highly Sensitive and Novel Method and Its Clinical Applications. Guo, R; Shaikh, AS, 2017)	2.18
"Phenytoin has been decreasingly used because of the high interindividual variability in drug concentration and the narrow therapeutic window. "	( Optimal Dosing Regimen of Phenytoin for Korean Epilepsy Patients: From Premature Babies to the Elderly. Chae, D; Guk, J; Kim, JH; Lee, SG; Park, K, 2019)	2.26
"Phenytoin has complex pharmacokinetics. "	( Phenytoin dosing and serum concentrations in paediatric patients requiring 20 mg/kg intravenous loading. Appleton, R; Hawcutt, DB; Newland, P; Piper, JD; Spinty, S; Verghese, GK, 2014)	3.29
"Phenytoin has a narrow therapeutic window, and when managing cases of toxicity, clinicians are very wary of this fact. "	( Free phenytoin toxicity. Gambhir, H; Imam, SH; John, D; Kaul, V; Kloss, B; Landry, K, 2014)	2.36
"Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). "	( The effect of polymorphic metabolism enzymes on serum phenytoin level. Ergeç, D; Gulcebi, MI; Guney, I; Onat, FY; Ozkara, C; Ozkaynakci, A; Ulucan, K; Uzan, M, 2015)	2.11
"Phenytoin has a narrow therapeutic window and seizures can occur at both ends of the spectrum."	( Paradoxical Seizure Response to Phenytoin in an Epileptic Heroin Addict. Dewberry, RG; Pula, T; Vasagar, B; Verma, BR, 2015)	2.14
"Phenytoin has positive effects on healing of mucosal and dermal wounds."	( Phenytoin mouthwash to treat cancer therapy-induced oral mucositis: A pilot studyPrimary neuroendocrine carcinoma of breast: A rare tumor. Ameri, A; Baharvand, M; Hamian, M; Moosavizadeh, MA; Mortazavi, A, )	2.3
"Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use."	( Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Wang, X; Xu, X; Yang, Y; Zheng, F, 2016)	1.47
"Phenytoin has been explored in over 100 different disorders; the last two promising indications tested in the clinic are breast cancer and optic neuritis."	( Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action. Keppel Hesselink, JM; Kopsky, DJ, 2017)	2.62
"Phenytoin has many known ill effects on the genitourinary system including acute interstitial nephritis, nephrotic syndrome, acute renal failure, and priapism."	( Phenytoin metabolite renal calculus: an index case. Bauer, R; Kalorin, CM; White, MD, 2008)	2.51
"Phenytoin has a narrow therapeutic range and exhibits concentration-dependent kinetics within this therapeutic window. "	( Elevated thyroid-stimulating hormone in a 65-year-old patient with phenytoin toxicity. Collins, RJ, 2008)	2.02
"Phenytoin has been an effective anticonvulsant agent for over 60 years, although its clinical use is complicated by nonlinear pharmacokinetics, a narrow therapeutic index, and metabolically based drug-drug interactions. "	( CYP2C9 amino acid residues influencing phenytoin turnover and metabolite regio- and stereochemistry. Mosher, CM; Rettie, AE; Tai, G, 2009)	2.06
"Phenytoin has been associated predominantly with bradyarrhythmias, some of which were fatal."	( Arrhythmia, heart rate variability, and antiepileptic drugs. Kennebäck, G; Tomson, T, 1997)	1.02
"Phenytoin has two important properties that are advantageous for assessing the validity of the theta suppression model: 1) it is a standard antiepileptic drug with no known anxiolytic effects, and 2) its primary mechanism of action is through suppression of the persistent sodium current, an effect that should also suppress hippocampal theta."	( A critical test of the hippocampal theta model of anxiolytic drug action. Dickson, CT; Treit, D; Yeung, M, 2012)	1.1
"Phenytoin has wound-healing promoting and collagenase inhibitory effects."	( Positive effects of phenytoin on experimental colonic anastomoses. Bulut, E; Canbay, E; Cetinkaya, O; Elagöz, S; Karadayi, K; Saraydin, SU; Sen, M; Turan, M, 2004)	1.37
"Phenytoin toxicity has ECG effects consistent with its mechanism as a sodium channel blocker."	( ECG features of sodium channel blockade in rodent phenytoin toxicity and effect of hypertonic saline. Cave, G; Sleigh, JW, 2003)	1.29
"Phenytoin has been causally implicated in three human cancers: lymphoma, myeloma and neuroblastoma, the latter specifically in the setting of foetal hydantoin syndrome."	( Cancer risk in people with epilepsy: the role of antiepileptic drugs. Driever, PH; Sander, JW; Singh, G, 2005)	1.05
"Phenytoin has been reported to have major interactions with warfarin. "	( The complexity of achieving anticoagulation control in the face of warfarin-phenytoin interaction: an Asian case report. Awaisu, A; Aziz, NA; Hassan, Y; Ismail, O, 2005)	2
"Phenytoin has not previously been studied prophylactically in bipolar patients."	( Phenytoin: an anti-bipolar anticonvulsant? Bersudsky, Y, 2006)	2.5
"Phenytoin has complicated non-linear kinetics, is highly protein bound and has a small window between its therapeutic and toxic dose."	( A case of phenytoin toxicity in a patient with advanced lung cancer. Jenkins, A, 2006)	1.46
"Phenytoin has been shown to induce serum IgA deficiency in patients with epilepsy. "	( The reversibility of phenytoin-induced IgA deficiency. Aarli, JA; Gilhus, NE, 1981)	2.02
"Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. "	( Phenytoin revisited. Finkel, MJ, 1984)	3.15
"Phenytoin also has been effective in some cases, suggesting that bulimia may be a neurologic disorder analogous to epilepsy."	( Treatment of bulimia. Conner, CS, 1983)	0.99
"Phenytoin has been widely prescribed alone; our results indicate that sodium valproate may also be used as a single drug in the treatment of several types of epilepsy."	( Comparison of sodium valproate and phenytoin as single drug treatment in epilepsy. Johnson, RH; Lambie, DG; Melville, ID; Nanda, RN; Shakir, RA, 1981)	1.26
"Phenytoin sodium has been associated with the formation of altered T lymphocyte rosettes in vitro. "	( Phenytoin and formation of T lymphocyte rosettes. Leppik, IE; Neilan, BA, 1980)	3.15
"Phenytoin has marked enzyme-inducing properties and can stimulate the metabolism of many concurrently administered drugs, thereby reducing their therapeutic efficacy."	( Drug interactions with phenytoin. Perucca, E; Richens, A, 1981)	1.29
"Phenytoin has been shown to cause choreiform movements, peripheral neuropathy, and cognitive decline in some patients, but the pathological basis for these changes has not been elucidated."	( Neuronal loss from the subthalamic nuclei in a patient with progressive chorea. Hedreen, JC; Sinard, JH, 1995)	1.01
"Phenytoin has previously been shown to protect against motion sickness induced by Coriolis stimulation. "	( Phenytoin for motion sickness: clinical evaluation. Chelen, W; Ferguson, R; Johnson, L; Knox, GW; Woodard, D, 1994)	3.17
"Phenytoin has been considered a possible cause of cerebellar degeneration, especially after clinical intoxication. "	( [Cerebellar atrophy and phenytoin poisoning. An MR study]. Aichner, F; Bauer, G; Birbamer, G; Felber, S; Luef, G; Marosi, M, 1993)	2.04
"Phenytoin has been associated with acute hepatotoxicity. "	( Phenytoin-induced chronic hepatitis. Levine, RA; Mahoney, HC; Roy, AK, 1993)	3.17
"Phenytoin has been shown to protect against motion sickness induced by Coriolis stress."	( Phenytoin as a countermeasure for motion sickness in NASA maritime operations. Chelen, W; Ferguson, B; Knox, G; Myers, KJ; Woodard, D, 1993)	2.45
"Fosphenytoin has fewer local adverse effects (e.g., pain, burning, and itching at the injection site) after i.m."	( Pharmacology and pharmacokinetics of fosphenytoin. Browne, TR; Eldon, MA; Kugler, AR, 1996)	1.08
"Phenytoin has been used in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, and burns. "	( Phenytoin in wound healing. Anstead, GM; Hart, LM; Liter, ME; Sunahara, JF, )	3.02
"Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility, which obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable phenytoin formulation."	( Safety of fosphenytoin sodium. Benezra, DA; Fierro, LS; Savulich, DH, 1996)	1.18
"Phenytoin has been observed to exert variable effects on dopamine metabolites and also may induce changes in serotonergic activity."	( Postural myoclonus induced by phenytoin. Cabezas, MC; Clavería, LE; Duarte, J; Marcos, J; Sempere, AP, 1996)	1.3
"1. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy, for over 50 years. "	( Basis of the antiseizure action of phenytoin. Tunnicliff, G, 1996)	1.19
"Fosphenytoin has been tested successfully for three indications in humans: intramuscular maintenance dosing, intramuscular loading dose administration, and intravenous treatment of status epilepticus."	( Fosphenytoin (Cerebyx). Browne, TR, 1997)	1.43
"Fosphenytoin has recently been approved as a substitute for parenteral phenytoin."	( New drug therapy for acute seizure management. Morton, LD; Pellock, JM; Rizkallah, E, 1997)	0.81
"Phenytoin has been reported to induce various hematologic reactions, including thrombocytopenia. "	( Phenytoin-induced thrombocytopenia. Holtzer, CD; Reisner-Keller, LA, 1997)	3.18
"Phenytoin has been identified as an alternative for the treatment of preeclampsia and the prevention of eclampsia."	( Phenytoin as an alternative treatment for preeclampsia. Jordan, ET; Lucas, LS, )	2.3
"Fosphenytoin has several advantages and disadvantages that should be considered when selecting its use in place of parenteral phenytoin."	( Fosphenytoin. Luer, MS, 1998)	1.44
"Phenytoin has been reported to exert variable anticonvulsant effects in the kindling model of complex partial seizures. "	( Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin. Ebert, U; Löscher, W; Reissmüller, E, 1998)	2.04
"Phenytoin has probably mutagenic potential effect on human sperm cells."	( [Effects of phenytoin on structural aberration of human sperm chromosomes in vitro]. Cui, X; Gao, X; Li, D; Meng, H; Wang, X; Wang, Z; Zhang, F, 2001)	2.13
"Phenytoin has no effect on clinafloxacin pharmacokinetics, while phenytoin clearance is 15% lower during clinafloxacin administration."	( Drug interactions with clinafloxacin. Abel, R; Alvey, CW; Bron, NJ; Hounslow, NJ; Koup, JR; Randinitis, EJ; Rausch, G; Sedman, AJ; Vassos, AB, 2001)	1.03
"Phenytoin (PHT) has been widely used intravenously for the treatment of seizures since 1956, and for many years, it has been considered first-line therapy for status epilepticus. "	( A prospective study of the incidence of the purple glove syndrome. Anandan, JV; Barkley, GL; Burneo, JG, 2001)	1.75
"Phenytoin has been reported to cause severe toxicity in PMs."	( Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Goldstein, JA, 2001)	1.03
"Phenytoin also has been used to treat bupivacaine cardiotoxicity."	( Bupivacaine-induced QRS prolongation is enhanced by lidocaine and by phenytoin in rabbit hearts. Kariya, N; Mazoit, JX; Pelle-Lancien, E; Simon, L, 2002)	1.27
"Phenytoin has been analysed polarographically after oxidation with alkaline permanganate to give benzophenone; the limit of detection was found to be 6 x 10(-6) microg ml(-1)."	( Polarographic determination of phenytoin and benzophenone (as impurity) in pharmaceutical preparations. Gazy, AA; Razak, OA; Wahbi, AM, 2002)	1.32
"Phenytoin has been the preferred drug for treating grand mal epilepsy for more than 40 years. "	( Summary of an International Symposium on phenytoin-induced teratology and gingival pathology. Dudley, KH; Hassell, TM; Hirsch, PF; Hutchens, LH; Johnston, MC; Moriarty, JD, 1979)	1.97
"Phenytoin has traditionally been used for both prophylaxis and acute treatment of alcohol withdrawal seizures. "	( Rational management of alcohol withdrawal seizures. Josephson, GW; Sabatier, HS, 1978)	1.7
"Phenytoin has been shown to inhibit catecholamine (CA) metabolism in vitro. "	( Phenytoin and cerebellar lesions. Similar effects on cerebral catecholamine metabolism. Snider, RS; Snider, SR, 1977)	3.14
"Phenytoin (PHT) has long been known to cause folate depletion with chronic use. "	( Phenytoin treatment and folate supplementation affect folate concentrations and methylation capacity in rats. Carl, GF; Eto, I; Furman, GM; Krumdieck, CL; Schatz, RA; Smith, ML, 1991)	3.17
"Phenytoin has been reported to alter the pharmacokinetics of a large number of drugs."	( Pharmacokinetic drug interactions with phenytoin (Part I). Evans, AM; Milne, RW; Nation, RL, 1990)	1.27
"Phenytoin has been reported to blockade the various Ca2+ channels."	( [A study on the protective mechanism of phenytoin in transient global ischemia]. Imaizumi, S; Kinouchi, H; Kurosawa, K; Suzuki, J; Yoshimoto, T, 1989)	1.27
"Phenytoin has been proposed in the management of patients with the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) of neurological origin who fail to respond to water restriction. "	( Lack of efficacy of phenytoin in the syndrome of inappropriate anti-diuretic hormone secretion of neurological origin. Decaux, G; Przedborski, S; Soupart, A, 1989)	2.04
"Phenytoin sodium has been used to treat muscle cramps of diverse causes, and is known to increase insulin sensitivity during long-term use. "	( Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy. Flier, JS; Kingston, WJ; Landsberg, L; Meneilly, GS; Minaker, KL; Moxley, RT; Rowe, JW; Young, JB, 1989)	3.16
"Phenytoin (PHT) has been suspected of having a mutagenic effect with chronic administration, but the existing evidence is equivocal. "	( Lack of sister chromatid exchange induction in phenytoin-treated patients with epilepsy. Garry, VF; Schaumann, BA; Winge, VB, )	1.83
"Phenytoin has been proposed for the treatment of certain dermatologic conditions involving connective tissue abnormalities. "	( Phenytoin modulates connective tissue metabolism and cell proliferation in human skin fibroblast cultures. Holness, R; Moy, LS; Tan, EM; Uitto, J, 1985)	3.15
"Phenytoin has been implicated as a causative agent in peripheral neuropathy, although structural changes in nerve have not been characterized. "	( Phenytoin neuropathy: structural changes in the sural nerve. Griggs, RC; Mendell, JR; Ramirez, JA; Warmolts, JR, 1986)	3.16
"Phenytoin has been reported not only to maintain the intra- and extracellular cation balance but blockade the Ca channel."	( [The effect of phenytoin on free fatty acid liberation and mononucleotide metabolism in transient ischemia]. Imaizumi, S; Kinouchi, H; Motomiya, M; Suzuki, J; Yoshimoto, T, 1988)	1.35
"Phenytoin has been proposed as a prophylaxis and treatment of these dysrhythmias, since it is thought to improve conduction in this setting."	( Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning. Callaham, M; Pentel, P; Schumaker, H, 1988)	2.44
"Oral phenytoin has been shown to be effective in the treatment of recessive dystrophic epidermolysis bullosa (EB). "	( Efficacy of systemic phenytoin in the treatment of junctional epidermolysis bullosa. Fine, JD; Johnson, L, 1988)	1.11
"Free phenytoin has been determined using micro-scale ultracentrifugation followed by analysis by EMIT. "	( Micro-scale ultracentrifugation as an alternative to ultrafiltration for the determination of the unbound fraction of phenytoin in human serum. Cunningham, C; Jack, L; Stewart, MJ; Watson, ID, 1986)	0.99
"Phenytoin has known immunosuppressive properties, and a recent pilot study has indicated that it may have a second line effect in rheumatoid arthritis (RA). "	( Comparison of phenytoin and gold as second line drugs in rheumatoid arthritis. Capell, HA; Fraser, SM; Hunter, JA; Richards, IM, 1987)	2.08
"Phenytoin has been reported to be particularly effective in the treatment of postoperative ventricular arrhythmias in children. "	( Frequency-dependent actions of phenytoin in adult and young canine Purkinje fibers. Rosen, MR; Spinelli, W, 1986)	2
"Phenytoin has a beneficial effect on wound healing and on the healing of bone fractures, while beta-aminopropionitrile (BAPN) has an adverse effect on both. "	( Effect of phenytoin and/or beta-aminoproprionitrile on a surgically induced periosteal wound. Kuebel, MA; Taylor, JJ; Yeager, VL, 1985)	2.11
"Phenytoin has been shown to reduce the excessive production of collagenase and thereby to diminish blistering of skin and mucous membranes and stricture formation of the oesophagus."	( [Therapy of esophageal stenoses in recessive epidermolysis bullosa dystrophica]. Anton-Lamprecht, I; Baldauf, G; Feurle, GE; Weidauer, H, 1985)	0.99

Actions

Phenytoin may inhibit bone resorption through its action on the transcription, synthesis, and/or secretion of the collagenolytic enzymes, collagenase and gelatinase. The increase in the threshold for generalized seizure activity (TGS) was used as the anticonvulsant effect.

Excerpt	Reference	Relevance
"Phenytoin promotes the proliferation of endogenous neural precursor cells in the ventricular-subventricular zone in the postnatal brain that help restore the oligodendroglial population."	( Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone. Campos-Ordonez, T; Galvez-Contreras, AY; Gonzalez-Castañeda, RE; Gonzalez-Perez, O; Vega-Riquer, JM, 2022)	2.89
"Phenytoin is known to cause conduction slowing."	( Fosphenytoin induced transient pendular nystagmus. Shaikh, AG, 2013)	1.73
"Phenytoin can produce significant dose-related toxicity because of its zero order pharmacokinetics and is an important issue in pediatric emergency medicine. "	( Phenytoin toxicity presenting as acute meningo-encephalitis in children. Gupta, V; Yadav, A; Yadav, TP, )	3.02
"Phenytoin appears to increase LPV clearance via CYP3A4 induction, which is not offset by the presence of low-dose RTV."	( Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. Bertz, RJ; Eron, JJ; Gaedigk, A; Kashuba, AD; Lim, ML; Min, SS; Robinson, M, 2004)	1.31
"Phenytoin can increase gingival overgrowth by stimulating the proliferation of connective tissue, which implies a novel way to hasten the healing process after MI."	( Phenytoin can accelerate the healing process after experimental myocardial infarction? Ji, WJ; Jiang, TM; Li, YM; Shi, R; Sun, XN; Zhou, X; Zhu, Y, 2006)	2.5
"Phenytoin caused an increase in the k2 peak facilitation in the high frequency domain."	( Screening for the effects of antiepileptic drugs on short term plasticity using a time efficient bioassay. Chen, LS; Courellis, SH; Gholmieh, GI, 2007)	1.06
"Phenytoin seemed to suppress penicillin-induced epileptiform activity by decreasing synaptic transmission."	( Effects of phenytoin on normal activity and on penicillin-induced bursting in the guinea pig hippocampal slice. Schneiderman, JH; Schwartzkroin, PA, 1982)	1.38
"Phenytoin did not enhance male dy2J/dy2J breeding success."	( Breeding and offspring rearing ability of C57BL/6J dystrophic mice. Silverman, H; Younger, LE, 1984)	0.99
"Phenytoin may thus cause the false-positive uptake of radiogallium in lymph nodes; this finding may also prove to have nosological importance in identifying patients at particular risk of the side-effects of this drug."	( Abnormal biodistribution of radiogallium in persons treated with phenytoin. Catz, Z; Lentle, BC; Penney, H; Starreveld, E; Turner, AR, 1983)	1.23
"Phenytoin induced increase in serum HDL levels should not yet be equated with protection against atherosclerosis."	( Increase of low serum concentrations of high-density lipoprotein (HDL) cholesterol in TIA-patients treated with phenytoin. Kaste, M; Muuronen, A; Neuvonen, PJ; Nikkilä, EA, )	1.06
"4. Phenytoin failed to increase P4501A in either C57BL/6 or ICR mice, as assessed by both immunoblot analysis and metabolic activities."	( Phenytoin induction of cytochrome P4502B in mice: effects on hexobarbital hydroxylase activity. Gelboin, HV; Kim, ND; Park, SS; Won, SM; Yoo, JK, 1993)	2.24
"kg-1 phenytoin. The increase in the threshold for generalized seizure activity (TGS) was used as the anticonvulsant effect and the increase in the total number of waves in the 11.5 to 30 Hz frequency band was taken as the EEG effect measure."	( Pharmacokinetic-pharmacodynamic modeling of the anticonvulsant and electroencephalogram effects of phenytoin in rats. Danhof, M; Della Paschoa, OE; Mandema, JW; Voskuyl, RA, 1998)	0.97
"Phenytoin produced a lower serum level than the same dose of its sodium salt."	( Systematic determination of the serum phenytoin level as an aid in the management of children with epilepsy. Gamstorp, I; Lilienberg, G; Norell, E, 1975)	1.25
"Phenytoin may inhibit bone resorption through its action on the transcription, synthesis, and/or secretion of the collagenolytic enzymes, collagenase and gelatinase."	( The effect of phenytoin on collagenase and gelatinase activities in UMR 106-01 rat osteoblastic osteosarcoma cells. Lee, HM; Ramamurthy, NS; Rifkin, BR; Vernillo, AT, 1990)	1.36
"Phenytoin may also increase the potential for neoplasm development by a direct interaction with cellular DNA and/or an indirect mechanism by immunosuppression."	( Effects of phenytoin and carbamazepine on human natural killer cell activity and genotoxicity in vitro. Coulombe, RA; Hincks, JR; Margaretten, NC; Warren, RP, 1987)	1.38

Treatment

The phenytoin treatment causes cerebellar defect and anemia. Post-pheny toin treatment biopsies showed decreased density of inflammation, increased melanin and increased HMB45 positive cells.

Excerpt	Reference	Relevance
"Phenytoin treatment further augmented these complications."	( Atherogenic Risk Factors among Young Indian Adults with Epilepsy on Treatment with Phenytoin: Need for Novel Therapeutic Strategies. Bobby, Z; Nisha, Y; Sangeetha, A; Wadwekar, V, )	1.08
"The phenytoin-treated group also showed an increased expression of MBP in the corpus callosum and better functional scores in the horizontal bar test."	( Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone. Campos-Ordonez, T; Galvez-Contreras, AY; Gonzalez-Castañeda, RE; Gonzalez-Perez, O; Vega-Riquer, JM, 2022)	2.64
"The phenytoin treatment causes cerebellar defect and anemia."	( The interplay of epilepsy with impaired mitophagy and autophagy linked dementia (MAD): A review of therapeutic approaches. Agrawal, M; Dhurandhar, Y; Panda, SP, 2022)	1.2
"Post-phenytoin treatment biopsies showed decreased density of inflammation, increased melanin and increased HMB45 positive cells together with an increased number of CD4 positive lymphocytes and decreased number of CD8 positive lymphocytes."	( Evaluation of the effect and mechanism of action of local phenytoin in treatment of vitiligo. Abdelwahed Gaber, M; Abdou, AG; Elnagar, A; Elnaidany, NF, 2017)	1.15
"Phenytoin treatment significantly decreased the hemoglobin, white blood cells, lymphocytes and mean corpuscular volume levels without affecting red blood cell, packed cell volume, neutrophils, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration when compared with the control rats."	( Kolaviron and vitamin E ameliorate hematotoxicity and oxidative stress in brains of prepubertal rats treated with an anticonvulsant phenytoin. Adedara, IA; Adeyemo, OA; Bakare, OS; Egun, C; Farombi, EO; Owoeye, O, 2014)	1.33
"Phenytoin-treated kindled animals were associated with learning and memory deficit, while tacrine supplementation improved memory deficit with increased seizure severity score."	( Adjuvant anticholinesterase therapy for the management of epilepsy-induced memory deficit: a critical pre-clinical study. Goel, RK; Mishra, A, 2014)	1.12
"Phenytoin and valproate treatments were stopped,and he was able to walk 7 days after the termination of therapy."	( Phenytoin toxicity in a patient receiving concomitant use of phenytoin and S-1 plus cisplatin chemotherapy for advanced gastric cancer. Amano, S; Fukino, N; Kano, H; Kawasaki, A; Kida, K; Kuboi, Y; Mimatsu, K; Oida, T, 2011)	2.53
"Phenytoin-treated wounds were also smaller at 1 to 6 weeks postoperatively than the control group wounds."	( Effect of sodium diphenylhydantoin on skin wound healing in rats. Dorsett-Martin, W; Habibipour, S; Joshi, P; Lineaweaver, WC; Oswald, TM; Zhang, F; Zhou, XC, 2003)	1.04
"Phenytoin treatment resulted in a significant decrease in PTSD symptoms as measured with the CAPS (mean score = 65 pretreatment vs. "	( Treatment of posttraumatic stress disorder with phenytoin: an open-label pilot study. Douglas Bremner, J; Heim, CM; Mletzko, T; Nemeroff, CB; Reed, L; Siddiq, S; Welter, S; Williams, C, 2004)	2.02
"Phenytoin treatment resulted in a significant 6% increase in right brain volume (p < 0.05)."	( Effects of phenytoin on memory, cognition and brain structure in post-traumatic stress disorder: a pilot study. Bremner, JD; Brummer, M; Heim, CM; Mletzko, T; Nemeroff, CB; Quinn, S; Reed, L; Siddiq, S; Welter, S; Williams, C, 2005)	1.44
"The phenytoin-treated group showed significantly smaller increases on the ACT, a mania self-report scale, than the placebo-treated group."	( Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Brown, ES; Cullum, CM; Dhanani, N; Frol, A; Hanczyc, M; Hukovic, N; Jeffress, J; Khan, DA; Larkin, GL; Liggin, JD; Mageto, Y; McEwen, BS; Rosenblatt, R; Stuard, G, 2005)	1.21
"Phenytoin treatment could promote type I collagen cross-linking level and ratio of type I/III collagen in the infarcted region and had no obvious side effect on interstitial collagen volume fraction, subtype ratio and distribution in non-infarcted region. "	( Phenytoin can accelerate the healing process after experimental myocardial infarction? Ji, WJ; Jiang, TM; Li, YM; Shi, R; Sun, XN; Zhou, X; Zhu, Y, 2006)	3.22
"In phenytoin-treated animals, however, the loss of RGCs was significantly reduced compared to vehicle-treated glaucomatous animals."	( Neuroprotection by sodium channel blockade with phenytoin in an experimental model of glaucoma. Hains, BC; Waxman, SG, 2005)	1.1
"Phenytoin-treated rats that were presented with changes in context as they transferred from the appetitive to the aversive task learned the avoidance response to levels substantially higher than drug-treated rats not presented with the contextual changes."	( Discrete and contextual cue alterations eliminate the instrumental appetitive-to-aversive transfer impairment in phenytoin-treated rats. Dina, BS; Garraghty, PE; McDowell, AL; Samuelson, DL, )	1.06
"Phenytoin pretreatment elicited similar effects, but it failed to block the delta 9-THC-induced convulsions."	( Central excitatory properties of delta 9-tetrahydrocannabinol and its metabolites in iron-induced epileptic rats. Karler, R; Turkanis, SA, 1982)	0.99
"Phenytoin treatment in vivo has no significant effect on T4 5'-deiodination in pituitary or liver homogenates either."	( Conversion of thyroxine to triiodothyronine in the anterior pituitary gland and the influence of this process on thyroid status. Breitbart, R; Kaplan, MM, 1984)	0.99
"Phenytoin treatment was associated with further decreases in serum IgA in patients with idiopathic epilepsy (p = 0.063) and secondary epilepsy (p = 0.008)."	( Effects of phenytoin on man's immunity. Evaluation of changes in serum immunoglobulins, complement, and antinuclear antibody. Bardana, EJ; Craig, S; Davies, GH; Gabourel, JD, 1983)	1.38
"Phenytoin treatment prevented the occurrence of convulsive and EEG seizures; however, lipid peroxidation was unaffected (16.5 +/- 4.1 units/gm)."	( Effect of phenytoin and corticosteroids on seizures and lipid peroxidation in experimental posttraumatic epilepsy. Triggs, WJ; Willmore, LJ, 1984)	1.39
"In a phenytoin-treated patient with osteomalacia, switching the drug regimen to phenobarbital led to prompt resolution of her symptoms and restoration of normal serum calcium and serum 25-hydroxyvitamin D values."	( Prompt resolution of osteomalacia by switching from phenytoin to phenobarbital. Hawker, CD; Meier, DA; Stoffer, SS, 1980)	0.97
"The phenytoin treated children did not differ with respect to the concentrations of IgA in saliva in comparison to the controls."	( Phenytoin and IgA concentrations in plasma and saliva in epileptic children. Falk, O; Modéer, T; Rane, A; Tomson, G, 1981)	2.19
"Phenytoin-treated embryos within 4 hr also demonstrated maximal 8-OH-2'-dG formation, which was substantially greater than that of controls, with a maximal 3-fold increase over controls at 24 hr (p < 0.05)."	( Phenytoin-initiated DNA oxidation in murine embryo culture, and embryo protection by the antioxidative enzymes superoxide dismutase and catalase: evidence for reactive oxygen species-mediated DNA oxidation in the molecular mechanism of phenytoin teratogen Wells, PG; Winn, LM, 1995)	2.46
"Phenytoin-treated patients had a significant reduction in the mean IgA and IgG levels compared to healthy and epileptic controls (P < 0.05)."	( Humoral and cellular immune parameters in untreated and phenytoin-or carbamazepine-treated epileptic patients. Başaran, N; Ciğer, A; Hincal, F; Kansu, E, 1994)	1.26
"Phenytoin treatment produced a significant downregulation in the level of expression for 25% of the genes examined in the GD 9:12 embryos, including the growth factors TGF-beta and NT3, the proto-oncogene Wnt-1, the nicotinic receptor, and the voltage sensitive calcium channel gene."	( Preliminary evidence of phenytoin-induced alterations in embryonic gene expression in a mouse model. Bennett, GD; Eberwine, JH; Finnell, RH; Greer, KA; Musselman, AC, )	1.16
"Phenytoin treatment was withdrawn, and calcitriol supplementation commenced."	( Abnormal bone mineral metabolism after long-term anticonvulsant treatment. Alderman, CP; Hill, CL, 1994)	1.01
"Phenytoin treatment caused a 63% decrease in hexobarbital sleeping time in ICR mice (19 versus 52 min)."	( Phenytoin induction of cytochrome P4502B in mice: effects on hexobarbital hydroxylase activity. Gelboin, HV; Kim, ND; Park, SS; Won, SM; Yoo, JK, 1993)	2.45
"The phenytoin-treated subjects with post-treatment measurements had a 0.24 g/l (8%) reduction in mean fibrinogen levels compared to placebo (p = 0.3)."	( Can phenytoin lower plasma fibrinogen concentrations? Folsom, A; Goerdt, C; Rubins, HB; Swaim, W, 1995)	1.33
"The phenytoin and placebo treatment groups did not differ in the number of tokens valued at $5, exchanged for cocaine."	( Effects of phenytoin on cocaine self-administration in humans. Bliss, RL; Goldman, AI; Hatsukami, DK; Pentel, PR; Sofuoglu, M, 1999)	1.17
"Phenytoin treatment for 48 h significantly increased the secretion of BMP-2 by approx."	( Evidence for the involvement of bone morphogenetic protein-2 in phenytoin-stimulated osteocalcin secretion in human bone cells. Kaku, T; Koyama, H; Nakade, O; Saitoh, T; Takuma, T, 2000)	1.27
"Phenytoin treatment showed no beneficial effects on mortality and was associated with a high incidence of side effects."	( Effect on survival after myocardial infarction of long-term treatment with phenytoin. Duffield, A; Harper, R; Hunt, D; Luxton, M; Peter, T; Ross, D; Sloman, G, 1978)	1.21
"Phenytoin-treated patients failed to manifest delayed hypersensitivity (DHS) reactions to common antigens, and to make antibody to Salmonella typhi and tetanus toxoid."	( Depression of immune competence by phenytoin and carbamazepine. Studies in vivo and in vitro. Forbes, IJ; Sorrell, TC, 1975)	1.25
"The phenytoin-treated group showed marked decrease in blister count, increase in trauma tolerance, a rise in hemoglobin level, and considerable weight gain."	( Recessive dystrophic epidermolysis bullosa treated with phenytoin. Abahussein, AA; al-Zayir, AA; Mostafa, WZ; Okoro, AN, 1992)	1.01
"Phenytoin treatment abolished the clinical signs of muscle fasciculations following oral potassium challenge and decreased or abolished repetitive firing and myotonic discharges found on electromyographic examination."	( Effects of phenytoin in two myotonic horses with hyperkalemic periodic paralysis. Beech, J; Fletcher, JE; Lindborgh, S; Tripolitis, L, 1992)	1.39
"Phenytoin pretreatment significantly reduced myalgia from 45% (nine patients) in the control group to 10% (two patients) (p less than 0.05)."	( Phenytoin reduces suxamethonium-induced myalgia. Hatta, V; Kaul, HL; Saxena, A, 1992)	2.45
"Phenytoin treatment caused a decrease in weight gain over the 8 wk of treatment."	( Phenytoin treatment and folate supplementation affect folate concentrations and methylation capacity in rats. Carl, GF; Eto, I; Furman, GM; Krumdieck, CL; Schatz, RA; Smith, ML, 1991)	2.45
"5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm."	( Factors in the lethality of i.v. phencyclidine in conscious dogs. Davis, WM; Hackett, RB; Obrosky, KW; Waters, IW, 1991)	0.8
"Phenytoin treatment was found to have differential effects on the in vitro production of Type I and Type II interferons."	( Effects of phenytoin on the production of interferons: differential effects on type I and type II interferons. Fields, EE; Fleischmann, WR; Ramarathinam, N, )	1.24
"Phenytoin treatment of inducible ventricular tachyarrhythmias was assessed by serial electrophysiologic studies (EPS) in 64 patients with spontaneous ventricular tachycardia, cardiac arrest, or symptoms compatible with a ventricular tachyarrhythmia. "	( Phenytoin in the treatment of inducible ventricular tachycardia: results of electrophysiologic testing and long-term follow-up. Epstein, AE; Henthorn, RW; Plumb, VJ; Waldo, AL, 1987)	3.16
"Phenytoin treatment may impair the validity of the caffeine liver function test."	( Effect of phenytoin, carbamazepine, and valproic acid on caffeine metabolism. Büchsel, R; Kohl, D; Kreiten, K; Matern, S; Wietholtz, H; Zysset, T, 1989)	1.4
"Phenytoin pretreatment provided significant protection from CA1 neuron loss in all groups tested (p less than 0.001), but the degree of protection varied from 20% to 44%."	( Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia. Blair, RE; Choi, SC; Clifton, GL; DeLorenzo, RJ; Taft, WC, 1989)	1
"All phenytoin-treated animals displayed a hepatomegaly."	( Degeneration of granule cells following chronic phenytoin administration: an electron microscopic investigation of the mouse cerebellum. Detmar, M; Kirchgässner, N; Volk, B, 1986)	1.01
"Phenytoin treatment resulted in higher liver ascorbic acid tissue levels than in controls."	( Alterations in tissue trace element and ascorbic acid metabolism in phenytoin-fed rats and mice. Dubick, MA; Keen, CL, 1985)	1.23
"The treatment with phenytoin under both control and stress conditions resulted in an inhibitory effect on cell proliferation, which was more evident in the heart than in the hippocampus. "	( Effect of phenytoin treatment on cell proliferation in the hippocampus and the heart and related neuroendocrine changes under non-stress and stress conditions. Babic, S; Jezova, D, 2014)	1.13
"Treatment with phenytoin even deepened stress-induced reduction of cell proliferation in the heart."	( Effect of phenytoin treatment on cell proliferation in the hippocampus and the heart and related neuroendocrine changes under non-stress and stress conditions. Babic, S; Jezova, D, 2014)	1.14
"Treatment with phenytoin induced localized CYP2E1 expression in the brain whereas no significant effects were exerted by carbamazepine or phenobarbital."	( Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression. Boussadia, B; de Bock, F; Ghosh, C; Janigro, D; Marchi, N; Pascussi, JM; Plaud, C; Rousset, MC, 2014)	0.74
"Treatment with phenytoin, at a dose equivalent to that used to treat epilepsy (60 mg/kg; daily), significantly reduced tumour growth, without affecting animal weight."	( The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis. Brackenbury, WJ; Dowle, AA; Nelson, M; Thomas, JR; Yang, M, 2015)	1.01
"Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control."	( Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants. Goel, RK; Singh, D; Singh, P, 2016)	1.09
"Pretreatment with phenytoin (5 mg/kg) in combination with SMF had significantly greater effects on seizure latency and severity than either pretreatment alone."	( Effects of a static magnetic field on audiogenic seizures in black Swiss mice. Engström, S; McLean, MJ; Polley, D; Polley, DB; Qinkun, Z; Spankovich, C, 2008)	0.67
"Treatment with phenytoin (PHT) almost immediately caused her speech and singing to return to baseline. "	( Expressive aprosody and amusia as a manifestation of right hemisphere seizures. Bautista, RE; Ciampetti, MZ, 2003)	0.67
"Pretreatment with phenytoin produced a significant increase in maternal lethality following caffeine administration but no co-teratogenic effect."	( The toxicology of chemical interactions during pregnancy in the mouse: caffeine and phenytoin. Kwasigroch, TE; Poche, PD; Skalko, RG, 1984)	0.82
"Treatment with phenytoin was effective in all cases."	( Focal paroxysmal kinesigenic choreoathetosis. Plant, G, 1983)	0.61
"Dogs treated with phenytoin (PHT) were clinically superior to untreated controls when compared 6 weeks after injury."	( Effect of phenytoin on functional recovery after experimental spinal cord injury in dogs. Gerber, AM; Harris, JH; Olson, WL, 1980)	0.99
"Treatment with phenytoin did not influence the results."	( Positron emission tomographic study of late-onset cryptogenic symptomatic seizures. Crevits, L; De Reuck, J; Decoo, D; Goethals, P; Lemahieu, I; Santens, P; Strijckmans, K; Van Maele, G, 1995)	0.63
"Treatment with phenytoin and carbamazepine produced only temporary improvement."	( Continuous muscle fibre activity (Isaacs' syndrome) in infancy: a report of two cases. Dubowitz, V; Heckmatt, JZ; Ransley, YF; Rodillo, E; Thomas, NH, 1994)	0.63
"Pretreatment with phenytoin and carbamazepine prevented a reduction of this activity, which, without either treatment, was observed in the cerebral hemisphere exposed to 30-minute ischemia resulting from unilateral middle cerebral artery occlusion."	( Effects of the conventional anticonvulsants, phenytoin, carbamazepine, and valproic acid, on sodium-potassium-adenosine triphosphatase in acute ischemic brain. Furui, T; Murakami, A, 1994)	0.87
"Treatment of phenytoin responders and nonresponders with other primary antiepileptic drugs showed that valproate and phenobarbital induced much smaller increases in focal seizure threshold in phenytoin nonresponders than in responders, whereas carbamazepine induced about the same threshold increase in both groups."	( Pharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy. Hönack, D; Löscher, W; Rundfeldt, C, 1993)	0.91
"Pretreatment with phenytoin or lidocaine did neither modify these values nor change the pattern of the arrhythmias or the terminal cardiac event."	( Influence of pretreatment with phenytoin, lidocaine and quinidine on the cardiodynamic and electrophysiological effects of ouabain in the cat heart-lung preparation. Simaan, JA, )	0.74
"Treated with phenytoin, carbamazepine and phenobarbital, seizures subsided but left choreic-like flinging movements, consistent with hemiballism, presented 2 days later."	( Hemiballism in a patient with partial motor status epilepticus treated with phenytoin. Asconape, J; Gatto, M; Lehkuniec, E; Micheli, F; Pelli, M, )	0.71
"Treatment with phenytoin caused a dramatic clinical improvement."	( Subclinical status epilepticus in a child after closed head injury. Beni, L; Constantini, S; Matoth, I; Pomeranz, S, 1996)	0.63
"Treatment with phenytoin (140 mg/kg) at 1200 h on day 28, which induces serum levels approximately twice those reached with the clinical dose as anticorvulsant drug for humans, was effective for inhibiting the first ovulation and normal secretion of serum follicle - stimulating hormone and luteinizing hormone (LH) on day 29 as well as the preovulatory gonadotrophin surge on day 28."	( Phenytoin inhibits both the first ovulation and uterine development in gonadotropin-primed immature rats. Abe, Y; Kogo, H; Tamura, K, 2000)	2.09
"Pretreatment with phenytoin, sodium methylprednisolone succinate and dexamethasone had little or no effect."	( The effect of phenobarbital pretreatment on the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea (PCNU), and on the plasma p Byrd, A; Finn, A; Levin, VA; Stearns, J; Weinkam, RJ, 1979)	0.58
"Treatment with phenytoin sodium resulted in rapid improvement of the peripheral symptoms and simultaneous resolution of the laryngeal spasm."	( Laryngeal spasm complicating pseudomyotonia. Canalis, RF; Kaplan, HJ; Levinson, S, 1976)	0.6
"Treatment with phenytoin or carbamazepine resulted in nearly complete resolution of symptoms in all five patients."	( Bradycardia and syncope as manifestations of partial epilepsy. Constantin, L; Dagli, RD; Fincham, RW; Martins, JB, 1990)	0.62
"Pretreatment with phenytoin significantly attenuated the tremor produced by p,p'-DDT but enhanced that produced by chlordecone."	( 5,5-Diphenylhydantoin antagonizes neurochemical and behavioral effects of p,p'-DDT but not of chlordecone. Hong, JS; Hudson, PM; Tilson, HA, 1986)	0.59
"Pretreatment with phenytoin, which is thought to bind to the inactivation gates of sodium, had no effect on the effects produced by lindane or kainic acid."	( The effects of lindane, DDT, and chlordecone on avoidance responding and seizure activity. McLamb, RL; Shaw, S; Tilson, HA, 1987)	0.6
"Treatment with phenytoin resulted in a significant increase in growth hormone release after diazepam and glucagon, whilst sodium valproate reduced the growth hormone response to diazepam."	( Growth hormone response to diazepam, clonidine and glucagon in patients with epilepsy. Belchetz, P; Chadwick, D; Crawford, PM; Davis, C, )	0.47
"Pretreatment with phenytoin, 20 mg/kg, reduced the number of fasciculations to 32% of control without altering contractile strength."	( Effects of calcium channel blocking agents on neostigmine-induced fasciculations. Dretchen, KL; Henderson, TR; Raines, A, 1989)	0.6
"Treatment with phenytoin (200 mg/kg) blocked the ischemia-induced neuronal death."	( Phenytoin protects against ischemia-produced neuronal cell death. Blair, RE; Clifton, GL; DeLorenzo, RJ; Taft, WC, 1989)	2.06
"Treatment with phenytoin resulted in a marked reduction in the frequency of the episodes."	( Concurrent hypnogenic and reflex paroxysmal dystonia. De Arbelaiz, R; Lehkuniec, E; Micheli, F; Paradiso, G; Torres, M, 1988)	0.61
"Pretreatment with phenytoin significantly reduced the tremor and hyperresponsiveness produced by p,p'-DDT and permethrin."	( Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin. Hong, JS; Mactutus, CF; Tilson, HA, 1985)	0.87

Toxicity

Phenytoin alone was not toxic to cells. Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenyto in when ora ora is needed.

Excerpt	Reference	Relevance
" Soon after the drug was introduced into clinical practice, gingival enlargement was noticed as a side effect and, despite much research effort, the etiology of this condition remains unknown."	( Side effects of diphenylhydantoin: a review. Keith, DA, 1978)	0.26
" Very rarely, the toxic neurological manifestations of this drug are of cerebral origin."	( Transient hemiparesis: a rare manifestation of diphenylhydantoin toxicity. Report of two cases. Findler, G; Lavy, S, 1979)	0.26
" Monitoring drug levels and electroencephalograms appears to be the method of choice for ensuring safe and effective medication in intractable epilepsy."	( Electroencephalography and phenytoin toxicity in mentally retarded epileptic patients. Helle, EP; Iivanainen, M; Seppäläinen, AM; Viukari, M, 1978)	0.56
" Other toxic manifestations included neurological side effects of a lethargic stupor, excitability to a disturbance, or a characteristic condition referred to as "head under."	( Toxicity and tissue residues from diphenylhydantoin fed to chickens. Polin, D; Ringer, RK, 1976)	0.26
" All patients were stabilized on diphenylhydantoin alone, and assessment of this drug by gas-liquid chromatography provided a basis for dichotomizing the group into High and Low drug groups, both with and without toxic patients."	( Diphenylhydantoin serum levels, toxicity, and neuropsychological performance in patients with epilepsy. Dodrill, CB, 1975)	0.25
" More common toxic effects were not noted on initial evaluation of the patient."	( Acute athetosis as a result of phenytoin toxicity in a child. Marks, RE; Zinsmeister, S, 1976)	0.54
"Rare, serious adverse effects of antiepileptic drugs (AEDs) include hepatotoxicity and bone marrow suppression."	( Routine laboratory monitoring for serious adverse effects of antiepileptic medications: the controversy. Wyllie, E; Wyllie, R, 1991)	0.28
" Although one of the first associations between anticonvulsant therapy and an adverse development effect in humans was noted in 1964 (104), the mechanism(s) whereby these adverse effects occur has thus far eluded research efforts."	( The embryotoxicity of phenytoin: an update on possible mechanisms. Hansen, DK, 1991)	0.6
"Intravenous succinylcholine (SCh) is widely used as a muscle relaxant but it is often associated with adverse effects, including muscle fasciculations, postoperative myalgia, elevated serum potassium (K+) and creatine phosphokinase (CPK), etc."	( [The study of pretreatment with diphenylhydantoin or D-tubocurarine on succinylcholine-induced adverse effects]. Ho, ST; Hu, OY; Hwing, CS; Kuo, WS; Li, CH, 1990)	0.28
"1% seizure control rate), with adverse effects of sedation and intellectual depression."	( Plasma level distribution, effect and toxicity of antiepileptic drugs among Ethiopian epileptics. Abebe, Y; Bekele, G; T'Haimanot, R, 1990)	0.28
" Other features of this adverse drug reaction were unremitting fever, leukocytosis with eosinophilia and atypical lymphocytosis, and proteinuria."	( Phenobarbital hepatotoxicity in an 8-month-old infant. Goldbach, M; Phillips, MJ; Roberts, EA; Spielberg, SP, 1990)	0.28
" Both were found to have toxic levels of Dilantin."	( Dilantin toxicity and vegetative depression: a report of two cases. Garrison, SJ; Henson, HK, 1990)	0.28
" Both p-HPPH and m-HPPH were much less developmentally toxic than DPH."	( Use of Frog Embryo Teratogenesis Assay-Xenopus and an exogenous metabolic activation system to evaluate the developmental toxicity of diphenylhydantoin. Bantle, JA; Fort, DJ, 1990)	0.28
" The severity of this adverse effect ranges from self-limiting to fatal."	( Phenytoin hepatotoxicity: a review of the literature. Smythe, MA; Umstead, GS, 1989)	1.72
"There is a narrow margin between therapeutic and toxic doses and serum levels of digitalis glycosides."	( Digitalis toxicity. Antman, EM; Smith, TW, 1985)	0.27
" Phenytoin is a relatively safe medication even in the toxic range as determined by baseline phenytoin levels."	( Phenytoin toxicity: a review of 94 cases. Curtis, DL; Ellenhorn, MJ; Ordog, G; Piibe, R; Wasserberger, J, 1989)	2.63
" These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations."	( Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution. Bittencourt, PR; Gorz, AM; Silvado, CE, 1986)	0.27
" Our study shows that VPA is a safe treatment in epileptic patients with PCT."	( Safety of valproate in porphyria cutanea tarda. Baldrati, A; Baruzzi, A; Benassi, G; Cassanelli, M; Cristina, E; D'Alessandro, R; Pizzino, D; Rocchi, E, )	0.13
" Indeed, although some form of side effect occurred in 50% of patients, treatment had to be changed in only 18% and the drug had to be stopped in only 7%."	( Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children. Armijo, JA; Arteaga, R; Herranz, JL, )	0.38
" However, carbamazepine consistently produced fewer adverse effects on tests of attention/concentration and motor performance than did the other three antiepileptic drugs."	( Results of a nationwide Veterans Administration Cooperative Study comparing the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Collins, JF; Craft, B; Cramer, JA; Mattson, RH; Novelly, RA; Smith, DB, 1987)	0.48
"Tricyclic antidepressants (TCA) are drugs with Type IA antiarrhythmic properties that cause severe cardiac conduction blocks, hypotension, and ventricular dysrhythmias at toxic levels."	( Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning. Callaham, M; Pentel, P; Schumaker, H, 1988)	1.72
"5 mg/kg, elevated the LD50 of diisopropylfluorophosphate (DFP) to a significant degree."	( Protection by phenytoin and calcium channel blocking agents against the toxicity of diisopropylfluorophosphate. Bowles, AM; Dretchen, KL; Raines, A, 1986)	0.63
" Concentrations of phenytoin considered therapeutic (10 and 20 micrograms/ml) and a dose considered acutely toxic (40 micrograms/ml) were used while carbamazepine levels of 8 micrograms/ml (therapeutic) and 10 and 16 micrograms/ml (acutely toxic) were tested."	( Effects of phenytoin and carbamazepine on human natural killer cell activity and genotoxicity in vitro. Coulombe, RA; Hincks, JR; Margaretten, NC; Warren, RP, 1987)	0.99
" These side effects were dose related: ventricular tachycardia appeared at a toxic serum phenytoin level in one patient and disappeared as the concentration fell within the therapeutic range, and atrioventricular block grade 1 developed in two patients at low serum carbamazepine levels, its severity increasing with the drug level."	( Cardiac side effects of phenytoin and carbamazepine. A dose-related phenomenon? Durelli, L; Glorioso, N; Gusmaroli, G; Monaco, F; Mutani, R; Sechi, GP, 1985)	0.8
" There is experimental evidence that the toxic action of phenytoin lies at the cellular level, predominantly in the cerebellum."	( Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Iivanainen, M; Savolainen, H, 1983)	0.79
" However, whereas toxic reactions following phenytoin and carbamazepine are characterised by a rather short duration of exposure before symptoms occur with accompanying clinical features of hypersensitivity, valproate-induced hepatic toxicity exhibits no signs of hypersensitivity and often occurs following prolonged exposure, speaking in favor of a metabolic aberration as the underlying cause."	( Hepatic toxicity of antiepileptic drugs: a review. Bentsen, KD; Gram, L, 1983)	0.53
"0 g of misonidazole, severe nausea and vomiting are prominent, so that this side effect is a determining factor in the treatment fractionation."	( The role of microsomal enzyme inducers in the reduction of misonidazole neurotoxicity. Bleehen, NM; Jones, DH; Smith, NC; Workman, P, 1983)	0.27
" Phenytoin alone was not toxic to cells."	( Predisposition to phenytoin hepatotoxicity assessed in vitro. Blake, DA; Goldstein, DA; Gordon, GB; Herlong, HF; Spielberg, SP, 1981)	1.51
" The comparison of hemodynamic, electrocardiographic and toxic effects of mexiletine with those produced by other antiarrhythmics showed that mexiletine placed itself among the better tolerated antiarrhythmics during the administration of progressively increasing doses."	( Hemodynamic, electrocardiographic and toxic effects of the intravenous administration of increasing doses of mexiletine in the dog. Comparison with similar effects produced by other antiarrhythmics. Carlier, J, 1980)	0.26
" Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole."	( Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin, tumor response and neurotoxicity. Dawes, PJ; Henk, JM; Moore, JL; Paterson, IC, )	0.61
"This study showed that the LD50 values for morphine sulfate, cobalt chloride, and phenytoin sodium did not vary significantly on Day 9 of gestation in CF-1 mice when compared to values of nongravid animals."	( Nonvariance of LD50 values of drugs in gravid and nongravid mice. Gautieri, RF; Mahalik, MP; McDevitt, JM; Russell, JA, 1980)	0.49
"6% of these had blood levels in the toxic range."	( Phenytoin toxicity due to concomitant antituberculosis therapy. Aboo, A; Walubo, A, 1995)	1.73
"Both groups had similar types and frequencies of mild to moderate adverse events."	( Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery. Campbell, K; Garnett, WR; Henkin, SA; Kugler, AR; Pellock, JM; Ramsay, RE; Wilder, BJ, 1996)	0.54
" Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible."	( Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery. Campbell, K; Garnett, WR; Henkin, SA; Kugler, AR; Pellock, JM; Ramsay, RE; Wilder, BJ, 1996)	0.87
" Adverse effects of antiepileptic treatment may affect the patient's quality of life to an even greater extent than the occurrence of seizures."	( Adverse effects of established and new antiepileptic drugs: an attempted comparison. Gram, L; Rogvi-Hansen, B, 1995)	0.29
"Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations."	( The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Boucher, BA; Dean, JC; Feler, CA; Kramer, RE; Kugler, AR; Michie, DD; Parks, BR; Smith, KR; Tipton, BK; Young, B, )	0.72
" Both routes are safe and well tolerated."	( The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Boucher, BA; Dean, JC; Feler, CA; Kramer, RE; Kugler, AR; Michie, DD; Parks, BR; Smith, KR; Tipton, BK; Young, B, )	0.38
" Within 3 weeks of beginning treatment with ticlopidine, he experienced acute clinical toxic effects of phenytoin with a maximum measured phenytoin concentration of 162."	( Acute phenytoin toxicity followed by seizure breakthrough from a ticlopidine-phenytoin interaction. Privitera, M; Welty, TE, 1996)	0.99
" Because of the potential for acute and permanent adverse effects from a drug-drug interaction, phenytoin concentrations should be carefully monitored when beginning or ending ticlopidine therapy."	( Acute phenytoin toxicity followed by seizure breakthrough from a ticlopidine-phenytoin interaction. Privitera, M; Welty, TE, 1996)	0.99
" Intravenous fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin."	( Safety of fosphenytoin sodium. Benezra, DA; Fierro, LS; Savulich, DH, 1996)	1.01
" AWD 140-190 thus presents an orally active and safe anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used."	( AWD 140-190: a new anticonvulsant with a very good margin of safety. Bartsch, R; Engel, J; Rostock, A; Rundfeldt, C; Tober, C; Unverferth, K; White, HS; Wolf, HH, 1997)	0.3
" The AM state in this patient was considered to be due to toxic DPH levels."	( Akinetic mutism due to diphenylhydantoin toxicity. Candan, C; Kantar, M; Tekgül, H; Tütüncüoğlu, S, )	0.13
" Adverse events associated with fosphenytoin generally were related to the central nervous system and were similar to those associated with phenytoin, except for a higher incidence of transient pruritus with fosphenytoin."	( Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy. Knapp, LE; Kugler, AR, 1998)	0.87
" PB was also the most toxic drug, followed by CBZ and by PHT."	( Anticonvulsant and neurotoxic effects of intracerebroventricular injection of phenytoin, phenobarbital and carbamazepine in an amygdala-kindling model of epilepsy in the rat. Alós, M; Barcia, JA; Belda, V; Rubio, P; Serralta, A, 1999)	0.53
" Two analyses of adverse events are presented: tolerability and safety."	( Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Bernstein, P; Faught, RE; Holmes, GL; Magnus-Miller, L; McLean, MJ; Morrell, MJ; Privitera, MD; Rose-Legatt, A; Willmore, LJ, 1999)	0.3
" Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only < or =1,800 mg/day (low dose); and (b) those reporting adverse events at only >1,800 mg/day (high dose)."	( Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Bernstein, P; Faught, RE; Holmes, GL; Magnus-Miller, L; McLean, MJ; Morrell, MJ; Privitera, MD; Rose-Legatt, A; Willmore, LJ, 1999)	0.3
"Gabapentin doses >1,800 mg/day were as well tolerated as doses < or =1,800 mg/day and were not associated with more adverse events."	( Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Bernstein, P; Faught, RE; Holmes, GL; Magnus-Miller, L; McLean, MJ; Morrell, MJ; Privitera, MD; Rose-Legatt, A; Willmore, LJ, 1999)	0.3
"The goals of this study were to determine if the use of phenytoin to prevent early posttraumatic seizures following head injury was associated with significant adverse side effects and also to determine if the reduction in early posttraumatic seizures after phenytoin administration was associated with a change in mortality rates in head-injured patients."	( Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. Dikmen, SS; Haltiner, AM; Newell, DW; Temkin, NR; Winn, HR, 1999)	0.8
" The incidence of adverse drug effects during the first 2 weeks of treatment, however, was low and not significantly different between the treated and placebo groups."	( Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. Dikmen, SS; Haltiner, AM; Newell, DW; Temkin, NR; Winn, HR, 1999)	0.56
" However, on rare occasions, they can progress to more severe cutaneous disorders, including Stevens-Johnson syndrome and toxic epidermal necrolysis."	( Therapeutic safety monitoring: what to look for and when to look for it. Harden, CL, 2000)	0.31
" We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use."	( Randomized evaluation of adverse events and length-of-stay with routine emergency department use of phenytoin or fosphenytoin. Clements, EA; Cochran, MS; Coplin, WM; O'Neil, BJ; Rebuck, JA; Rhoney, DH, 2002)	0.53
" It can cause generalized cutaneous eruptions that include a maculopapular exanthem, Stevens-Johnson syndrome, generalized exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, and fixed-drug eruptions."	( Phenytoin in cutaneous medicine: its uses, mechanisms and side effects. Scheinfeld, N, 2003)	1.76
" Further study is warranted to establish whether hypertonic saline has a role in treating phenytoin's toxic cardiac effects."	( ECG features of sodium channel blockade in rodent phenytoin toxicity and effect of hypertonic saline. Cave, G; Sleigh, JW, 2003)	0.79
" All adverse events were recorded."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	0.59
" All treatments were well tolerated: most adverse events were mild/moderate and transient."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	0.59
" Serum free-phenytoin concentration revealed toxic levels of phenytoin and no other etiology for retinopathy or optic neuropathy."	( Acute visual dysfunction following phenytoin-induced toxicity. Deleu, D; Shenoy, R; Thakral, A, 2003)	0.97
" So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system."	( Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray. Hwang, JW; Hwang, SY; Jeon, KS; Jung, JW; Kang, JS; Kang, KS; Kim, YS; Lee, GJ; Lee, WS; Lee, YS; Li, P; Oh, MJ; Park, JE; Park, JS; Song, BS; Um, CH; Yeo, CD; Youn, JP, 2004)	0.57
"Some of the more striking expressions of toxicity are the tremors and seizures observed approximately 100 min after exposure of rats to an acutely toxic dose of acrylonitrile (AN)."	( Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of acrylonitrile. Benz, FW; Nerland, DE, 2005)	0.33
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."	( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling. Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004)	0.32
" They were followed over 6 months with the primary outcome measure being treatment failure (either discontinuation or modification of AEDs) due to either adverse effects or breakthrough seizures."	( Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas. Chopra, SC; Kaushal, S; Rani, A; Singh, G, 2006)	0.6
"2%) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation."	( Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas. Chopra, SC; Kaushal, S; Rani, A; Singh, G, 2006)	0.99
"Clobazam was well tolerated, safe and more effective than phenytoin in the AED treatment of patients with SCG."	( Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas. Chopra, SC; Kaushal, S; Rani, A; Singh, G, 2006)	0.85
" Phenytoin has complicated non-linear kinetics, is highly protein bound and has a small window between its therapeutic and toxic dose."	( A case of phenytoin toxicity in a patient with advanced lung cancer. Jenkins, A, 2006)	1.65
" Our results indicate that it is possible to estimate LOEDs by integrating in vitro toxicity data as surrogates for lowest observed target tissue levels with PBBK models, provided that some knowledge about toxic mechanisms is known."	( Integration of in vitro neurotoxicity data with biokinetic modelling for the estimation of in vivo neurotoxicity. Blaauboer, B; Forsby, A, 2007)	0.34
" Administration of 300 mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33 microg/ml."	( Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Chandrasekaran, A; Chanolean, S; Narayan, SK; Ramasamy, K, )	0.59
"Abdominal distension and ileus may be presenting symptoms in children at toxic phenytoin levels."	( Unusual presentation of iatrogenic phenytoin toxicity in a newborn. DeGreeff, J; Lowry, JA; Scalzo, AJ; Vandover, JC, 2005)	0.83
"Idiosyncratic hepatotoxicity is a well-known complication associated with aromatic antiepileptic drugs (AAED), and it has been suggested to occur due to the accumulation of toxic arene oxide metabolites."	( Aromatic antiepileptic drugs and mitochondrial toxicity: effects on mitochondria isolated from rat liver. Curti, C; Martins, NM; Medina, WS; Mingatto, FE; Santos, AC; Santos, NA, 2008)	0.35
" However, the clinical use of these drugs is limited by several adverse effects, mainly idiosyncratic hepatotoxicity."	( Involvement of oxidative stress in the hepatotoxicity induced by aromatic antiepileptic drugs. Curti, C; Martins, NM; Medina, WS; Rodrigues, MA; Santos, AC; Santos, NA, 2008)	0.35
" Causes of the patient's toxic phenytoin concentration such as drug interactions, decreased albumin, and lab error were excluded."	( Phenytoin toxicity due to genetic polymorphism. Bullock, MR; McCluggage, LK; Voils, SA, 2009)	2.08
" Pharmacist drug counseling can help patients and family members identify adverse effects and toxicity and know when to seek medical assistance."	( Elevated thyroid-stimulating hormone in a 65-year-old patient with phenytoin toxicity. Collins, RJ, 2008)	0.58
" The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma."	( Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study. Barbaro, N; Burt, M; Chakalian, L; Chang, E; Chang, S; Lamborn, KR; Lim, DA; McDermott, MW; Tarapore, P, 2009)	0.62
"Severe cardiac adverse effects are often related to intravenous phenytoin overdose."	( Life-threatening cardiotoxicity due to chronic oral phenytoin overdose. Kung, CT; Lu, CH; Su, CM; Wang, YC, )	0.62
"Antiepileptic drugs (AEDs) have been widely used in patients with epilepsy but the adverse effects in adult Chinese patients have not been investigated."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.64
" An adverse effect profile, as well as efficacy of monotherapy, was obtained through a face-to-face interview with the patient at each visit."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.64
" Overall, 18% of patients experienced adverse effects: for CBZ (25/168; 14."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.64
" No fatal adverse events occurred."	( Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Wang, X; Xi, Z; Yan, Y; Zeng, K, 2010)	0.64
" 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
"8%) and due to adverse events (13."	( Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: a randomized double-blind clinical trial. Faught, E; Hulihan, J; Krumholz, A; Mao, L; Naritoku, D; Privitera, M; Ramsay, E; Schwarzman, L; Wiegand, F, 2010)	0.59
"Co-administration of phenytoin and oxcarbazepine resulted in toxic levels of phenytoin."	( Phenytoin toxicity secondary to an oxcarbazepine-phenytoin 2C19 interaction. Kane, AJ; Soskin, DP; Stern, TA, )	1.89
"  We identified significant associations of CYP2C9 variant alleles with presence of phenytoin (PHT) adverse drug reactions (ADRs) and of GSTM1 copy number variation with the presence of carbamazepine ADRs."	( A candidate gene study of antiepileptic drug tolerability and efficacy identifies an association of CYP2C9 variants with phenytoin toxicity. Da Cruz, AL; Depondt, C; Espel, RS; Godard, P; Lienard, P; Pandolfo, M, 2011)	0.8
"Thermodysregulation, including hypothermia, is recognized as a potential adverse effect secondary to atypical antipsychotics."	( Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient. Brandon Bookstaver, P; Miller, AD, 2011)	0.61
" Hypothermia should be recognized as a potential adverse event with the long-acting injectable formulation of risperidone."	( Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient. Brandon Bookstaver, P; Miller, AD, 2011)	0.61
"In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.37
" The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.37
"Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin."	( Side effects of phenobarbital in epilepsy: a systematic review. Li, YP; Zeng, LN; Zhang, LL, 2011)	0.56
" Hence intravenous valproate is safe and efficacious, with less time to regain consciousness."	( Comparative efficacy and safety of intravenous valproate and phenytoin in children. Aggarwal, A; Mittal, H; Rai, A; Sharma, S, 2011)	0.61
" Nevertheless, although the association of these genes with PTH-induced adverse effects has been well-documented in adult populations, this is the first report examining the influence of these genetic polymorphisms on PTH plasma levels and toxicity in a pediatric patient."	( Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms. Dorado, P; Llerena, A; López-Torres, E; Martínez-Antón, J; Peñas-Lledó, EM, 2013)	0.68
" This study aims to compare the tolerability, safety, and side effect profiles of levetiracetam (LEV) against the standard agent phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting."	( Tolerability, safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: a prospective randomized study. Cook, MJ; D'Souza, WJ; Fuller, KL; Murphy, MA; Wang, YY, 2013)	0.83
" Primary tolerability end points were discontinuation because of side effect and first side effect."	( Tolerability, safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: a prospective randomized study. Cook, MJ; D'Souza, WJ; Fuller, KL; Murphy, MA; Wang, YY, 2013)	0.63
" Comparative safety and differing side effect profile of intravenous LEV supports use as an alternative to intravenous PHT."	( Tolerability, safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: a prospective randomized study. Cook, MJ; D'Souza, WJ; Fuller, KL; Murphy, MA; Wang, YY, 2013)	0.63
"Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE."	( Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. Atabaki, SM; He, J; Herr, D; Klein, P; Levine, Z; McCarter, R; Natale, J; Nogay, C; Pearl, PL; Sandoval, F; Soldin, SJ; Trzcinski, S; Tsuchida, T; van den Anker, J, 2012)	0.38
" The most common adverse events were fatigue, headache, and somnolence."	( Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. Atabaki, SM; He, J; Herr, D; Klein, P; Levine, Z; McCarter, R; Natale, J; Nogay, C; Pearl, PL; Sandoval, F; Soldin, SJ; Trzcinski, S; Tsuchida, T; van den Anker, J, 2012)	0.38
"Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies."	( Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. Atabaki, SM; He, J; Herr, D; Klein, P; Levine, Z; McCarter, R; Natale, J; Nogay, C; Pearl, PL; Sandoval, F; Soldin, SJ; Trzcinski, S; Tsuchida, T; van den Anker, J, 2012)	0.38
" Decreased metabolism leads to higher plasma levels, causing adverse drug reactions (ADRs)."	( Association of CYP2C9 polymorphisms with phenytoin toxicity in Indian patients. Bendkhale, SR; Gogtay, NJ; Taur, SR; Thakkar, AN; Thatte, UM, )	0.4
" We found a significant association between polymorphic alleles CYP2C9 FNx01 2 and FNx013 and toxic phenytoin levels."	( Association of CYP2C9 polymorphisms with phenytoin toxicity in Indian patients. Bendkhale, SR; Gogtay, NJ; Taur, SR; Thakkar, AN; Thatte, UM, )	0.61
" We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI."	( Prediction of clinically relevant safety signals of nephrotoxicity through plasma metabolite profiling. Bush, ED; Fabian, E; Herold, M; Kamp, HG; Krennrich, G; Looser, R; Mattes, WB; Mellert, W; Moeller, N; Nadanaciva, S; Naraoka, H; Omura, K; Piccoli, SP; Prokoudine, A; Ruiz-Noppinger, P; Schuppe-Koistinen, I; Strauss, V; van Ravenzwaay, B; Walk, T, 2013)	0.39
" However, hepatotoxicity is one of its adverse effects reported in some patients."	( Mechanisms of phenytoin-induced toxicity in freshly isolated rat hepatocytes and the protective effects of taurine and/or melatonin. Eghbal, MA; Sattari, MR; Taziki, S, 2014)	0.76
" Risk of clinical and/or electrographic seizures, and risk of adverse drug events were compared between the two exposure arms."	( Levetiracetam versus phenytoin: a comparison of efficacy of seizure prophylaxis and adverse event risk following acute or subacute subdural hematoma diagnosis. Chou, SH; Du, R; Lee, JW; Radic, JA, 2014)	0.72
" Levetiracetam is associated with a lower risk of adverse drug effects."	( Levetiracetam versus phenytoin: a comparison of efficacy of seizure prophylaxis and adverse event risk following acute or subacute subdural hematoma diagnosis. Chou, SH; Du, R; Lee, JW; Radic, JA, 2014)	0.72
"Phenytoin (PHT), an anticonvulsant agent, widely used for the treatment of epilepsy has been reported to exhibit toxic side effects."	( Kolaviron and vitamin E ameliorate hematotoxicity and oxidative stress in brains of prepubertal rats treated with an anticonvulsant phenytoin. Adedara, IA; Adeyemo, OA; Bakare, OS; Egun, C; Farombi, EO; Owoeye, O, 2014)	2.05
" This case highlights that nutmeg, a spice, can cause serious toxic effects like status epilepticus."	( Myristicin and phenytoin toxicity in an infant. David, HS; Rajavelu, KK; Sampath, S; Sivathanu, S, 2014)	0.76
" One patient experienced apnea and oral dyskinesia as adverse effects of fPHT, whereas arrhythmia, hypotension, obvious reduction of consciousness, local irritation, phlebitis and purple grove syndrome were not observed in any patient."	( Efficacy and safety of fosphenytoin for acute encephalopathy in children. Akasaka, M; Hasegawa, T; Ishidou, Y; Kikuchi, K; Nakazawa, M; Niijima, S; Okumura, A; Shima, T; Shimizu, T; Suzuki, T; Takanashi, J; Yamamoto, A, 2015)	0.72
"We observed that in patients with traumatic brain injury (TBI) who did not improve as expected, serum levels of phenytoin were in the toxic range and that their sensorium improved with modification of the dose."	( Phenytoin toxicity in patients with traumatic brain injury. Abraham, AP; Joseph, M; Lakshmanan, J; Nair, S; Vidyasagar, A, )	1.79
"The safe use of medications in pregnant females, their embryos and in offspring is important."	( A toxicology study to evaluate the embryotoxicity of metformin compared with the hypoglycemic drugs, the anticancer drug, the anti-epileptic drug, the antibiotic, and the cyclo-oxygenase (COX)-2 inhibitor. Chai, Z; Li, L; Liu, C; Shen, X; Wang, L; Zhang, X; Zhang, Z, 2015)	0.42
"Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
" Once the drug has been absorbed, there are few methods that help decrease morbidity and mortality caused by a toxic drug level."	( Novel method for rapid reversal of drug toxicity: a case report. Bhangal, R; Poothencheri, S; Tatlow, C; Tatlow, D, 2015)	0.42
" Adverse effects of fosphenytoin, excessive sedation, or intravenous fluid incompatibility were not observed in any patients."	( Efficacy and safety of fosphenytoin for benign convulsions with mild gastroenteritis. Abe, S; Igarashi, A; Ikeno, M; Nakahara, E; Nakazawa, M; Niijima, S; Okumura, A; Shimizu, T; Toda, S; Yamashita, S, 2015)	1.03
" This article reviews the contribution of genetic polymorphisms affecting the activity of CYP2C9, the main enzyme responsible for phenytoin metabolism, to the variation in phenytoin clearance and susceptibility to adverse effects."	( CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Franco, V; Perucca, E, 2015)	0.93
" Patients carrying CYP2C9 genotypes associated with reduced phenytoin clearance are at greater risk of developing CNS adverse effects as well as serious cutaneous adverse reactions when given usual dosages of phenytoin."	( CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Franco, V; Perucca, E, 2015)	0.96
" Adverse effects of fosphenytoin may include: cardiovascular events (hypotension, arrhythmias), paresthesias or pruritus or some central events - somnolence, headache, dizziness, nystagmus and ataxia."	( The safety and efficacy of fosphenytoin for the treatment of status epilepticus. Borowicz, KK; Czuczwar, SJ; Popławska, M, 2015)	1.02
"Gum hypertrophy is a well-known and important adverse effect of phenytoin therapy in a neurosurgical patient."	( A well known and important adverse effect of phenytoin in a neurosurgical patient. Goyal, K; Kumar, N; Saxena, A; Tomar, GS, 2015)	0.92
" Serum concentrations of free phenytoin were determined, and adverse events were assessed at 0, 10, 20 minutes, and 24 hours after the infusion of fosphenytoin."	( Safety, Tolerability, and Pharmacokinetics of Fosphenytoin Loading in Patients With Subarachnoid Hemorrhage. Chun, YI; Ji, M; Kim, DW; Kim, TE, )	0.67
"Four patients experienced transient lowering of blood pressure, but other adverse events were not observed."	( Safety, Tolerability, and Pharmacokinetics of Fosphenytoin Loading in Patients With Subarachnoid Hemorrhage. Chun, YI; Ji, M; Kim, DW; Kim, TE, )	0.39
"Doxorubicin (DOX) is an effective anticancer agent, but adverse cardiotoxic effects limit its use."	( Cardioprotective Effect of Phenytoin on Doxorubicin-induced Cardiac Toxicity in a Rat Model. Asadnasab, G; Ashrafi Helan, J; Azarmi, Y; Babaei, H; Mohajjel Nayebi, A; Razmaraii, N, 2016)	0.73
" However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs."	( Cardiovascular adverse effects of phenytoin. Guldiken, B; Noachtar, S; Rémi, J, 2016)	0.94
" Clinical examination was performed for every patient, and seizure number, antiepileptic medication, and adverse events were detailed at every visit."	( Efficacy and safety of levetiracetam in the management of seizures in neonates. Asadi, F; Moradian, M; Moradian, N; Sedighi, M; Vakiliamini, M, 2016)	0.43
" In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin."	( Phenytoin: neuroprotection or neurotoxicity? Keppel Hesselink, JM; Kopsky, DJ, 2017)	2.12
" Only patients displaying persistent seizures or suspected of adverse effects were requested for drug monitoring."	( Analysis of phenytoin drug concentration for evaluation of clinical response, uncontrolled seizures and toxicity. Cao, L; Guo, R; Li, Y; Shaikh, AS, 2018)	0.86
"Dyskinetic neurological diseases are common presentations of adverse reaction to many therapeutic agents."	( Phenytoin Induced Chorea: A Rare Adverse Effect of the Drug. Gurumukhani, JK; Patel, DM; Patel, GR; Patel, MV, 2019)	1.96
" This is only the ninth case reported in literature regarding this rare and potentially serious adverse effect of levetiracetam."	( Rhabdomyolysis: a rare adverse effect of levetiracetam. Ahmed, N; Mirza, MMF; Shaikh, NA; Thomas, L, 2019)	0.51
" In this work, we propose to infuse a competitor drug into the extracorporeal circuit that increases the free fraction of a toxic drug and thereby increases its dialytic removal."	( A model-based analysis of phenytoin and carbamazepine toxicity treatment using binding-competition during hemodialysis. Fuertinger, DH; Hoffman, RS; Kotanko, P; Maheshwari, V; Tao, X; Thijssen, S, 2020)	0.86
" The secondary outcomes included application of an additional second-line AED, induction of anesthesia, and admission to the intensive care unit (ICU), and drug-related adverse reactions."	( Efficacy and safety profile of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children. Besli, GE; Yilmaz, S; Yuksel Karatoprak, E, 2020)	0.8
" Drug-related adverse reactions were more frequent in the phenytoin group than the levetiracetam group (23."	( Efficacy and safety profile of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children. Besli, GE; Yilmaz, S; Yuksel Karatoprak, E, 2020)	1.04
" Greater familiarity with the potential effects of TIPS on drug metabolism may help emergency physicians prevent adverse drug effects and optimize clinical outcomes."	( Phenytoin Toxicity After Transjugular Intrahepatic Portosystemic Shunt (TIPS). Aminlari, A; Bassell, T; Del Rosso, J; Hayden, S; Ly, BT, 2021)	2.06
"Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam."	( Efficacy and Safety of Phenobarbitone as First-Line Treatment for Neonatal Seizure: A Systematic Review and Meta-Analysis. Kumar, J; Meena, J; Saini, L; Yadav, J, 2021)	0.85
"6 million adverse event reports made to the FDA Adverse Event Reporting System (FAERS) database between July 1, 2018 and March 31, 2020 for DILI due to ASMs commonly used in clinical practice."	( Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS). Catalano, C; Gupta, K; Kamitaki, BK; Minacapelli, CD; Rustgi, V; Wachuku, C; Zhang, P, 2021)	0.62
"LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events."	( [Efficacy and safety of levetiracetam versus phenytoin as second-line drugs for the treatment of children with convulsive status epilepticus: a Meta analysis]. Shi, R; Wang, ZZ; Yin, HQ, 2021)	0.88
"We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia."	( Cosmetic adverse effects of antiseizure medications; A systematic review. Asadi-Pooya, AA; Mirzaei Damabi, N; Rostaminejad, M; Zeraatpisheh, Z, 2021)	0.62
" The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects."	( Cosmetic adverse effects of antiseizure medications; A systematic review. Asadi-Pooya, AA; Mirzaei Damabi, N; Rostaminejad, M; Zeraatpisheh, Z, 2021)	0.85
"Antiseizure medications may be associated with various cosmetic adverse effects."	( Cosmetic adverse effects of antiseizure medications; A systematic review. Asadi-Pooya, AA; Mirzaei Damabi, N; Rostaminejad, M; Zeraatpisheh, Z, 2021)	0.62
" The PubMed, Web of Science, Cochrane Library, and Embase databases were searched to identify eligible articles reporting outcomes including clinical seizure cessation within 60 min, clinical recurrence rate within 24 h, good final outcome at discharge, and adverse events (AEs) of treatment with levetiracetam and phenytoin."	( Comparison of the efficacy and safety of levetiracetam and phenytoin in the treatment of established status epilepticus: A systematic review and meta-analysis. Cui, XH; Dong, XZ; Liu, JM; Liu, WN; Yang, L; Zhang, L, 2021)	1.04
" However, the strong toxic effects limit its clinical application, and should be first considered."	( Central inhibition prevents the in vivo acute toxicity of harmine in mice. Gao, S; Li, J; Li, X; Liang, H; Lv, Y; Tang, X; Wang, M; Xiao, L; Zhang, J; Zou, H, 2021)	0.62
" However, published studies on the toxic effects of PHE at environmentally relevant concentrations in aquatic organisms are scarce."	( Multi-biomarker approach to evaluate the neurotoxic effects of environmentally relevant concentrations of phenytoin on adult zebrafish Danio rerio. Cardoso-Vera, JD; Elizalde-Velázquez, GA; Galar-Martínez, M; García-Medina, S; Gómez-Oliván, LM; Heredia-García, G; Islas-Flores, H; Orozco-Hernández, JM; Rosales-Pérez, KE, 2022)	0.93

Pharmacokinetics

Pharmacokinetic of propranolol, phenytoin and lidocain was studied in groups of male "Fauve de Bourgogne" rabbits. The findings suggested that the genetic polymorphism of CYP2C isoenzymes plays an important role in the pharmacokinetic variability of pheny toin.

Excerpt	Reference	Relevance
" It is suggested that more emphasis be given to general pharmacokinetic principles in drug information programs."	( Doses and dosage intervals of drugs--clinical practice and pharmacokinetic principles. Boëthius, G; Sjöqvist, F, 1978)	0.26
" However, the apparent elimination half-life (t 1/2) for MIS was reduced by 20-67%, and the area under the curve (AUC) was decreased by 23-49% in plasma, brain and tumour."	( Effects of pretreatment with phenobarbitone and phenytoin on the pharmacokinetics and toxicity of phenytoin on the pharmacokinetics and toxicity of misonidazole in mice. Workman, P, 1979)	0.52
"Anticonvulsant therapy was among the first areas to benefit from clinical pharmacokinetic studies."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
"A digital computer curve-fitting method, designed to estimate pharmacokinetic model constants by utilizing all drug concentration-time data collected during repetitive dosing studies, was applied to data manifesting systematic dose-to-dose variability in one or another of the pharmacokinetic parameters."	( Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration. Colburn, WA; Gibaldi, M, 1977)	0.26
"The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks."	( Pharmacokinetic observations of phenytoin disposition in the newborn and young infant. Aranda, JV; Greenwald, A; Loughnan, PM; Neims, AH; Purton, WW; Watters, G, 1977)	0.83
" No significant differences were seen in the pharmacokinetic parameters observed for antipyrine, a drug which is less than 10% bound to plasms proteins."	( Pharmacokinetics of drugs in patients with the nephrotic syndrome. Azarnoff, DL; Cohlmia, JB; Gugler, R; Huffman, DH; Shoeman, DW, 1975)	0.25
" The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS."	( Pharmacokinetic interaction of zonisamide in rats. Effect of other antiepileptics on zonisamide. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1992)	0.28
" Through pharmacokinetic analyses, the decreased AUC and increased Vz/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered."	( Effect of single- and multiple-dose carbamazepine on the pharmacokinetics of diphenylhydantoin. Huang, JD; Lai, ML; Lin, TS, 1992)	0.49
" This equation predicts the AUC0-INF produced by a given tracer dose of drug will vary directly with C in drugs with nonlinear pharmacokinetic properties (i."	( Bioavailability studies of drugs with nonlinear pharmacokinetics: I. Tracer dose AUC varies directly with serum concentration. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Schumacher, GE; Szabo, GK, 1992)	0.28
"To study possible pharmacokinetic interactions between two compounds a single-dose or a multiple dose experimental design may be used."	( The importance of prospective planning of pharmacokinetic trials. Considerations of studies on the phenytoin-digoxin-(P-D) and phenytoin-digitoxin-(P-DT) interaction. Rameis, H, 1992)	0.5
" Pharmacokinetic dose prediction methods have been developed allowing individual dosage adaptation."	( Therapeutic drug monitoring and pharmacokinetic dose prediction methods. Oellerich, M, 1992)	0.28
"A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients."	( Increased teniposide clearance with concomitant anticonvulsant therapy. Baker, DK; Christensen, ML; Evans, WE; Pui, CH; Relling, MV; Rodman, JH, 1992)	0.28
" A pharmacokinetic profile after a single oral 400-mg dose of ADD 94057 was used to calculate ADD 94057 dosages."	( Pharmacokinetic and dose tolerability study of ADD 94057 in comedicated patients with partial seizures. Cereghino, JJ; Laxer, KD; Manning, LW; McCormick, C; Pledger, GW; Sahlroot, JT; Taylor, MR; Whitley, L, )	0.13
" Regression of pharmacokinetic parameters with embryo and maternal endpoints indicated significant associations between gestational weight gain and maximum concentration measured (Cmax) or AUC in both strains."	( Phenytoin teratogenicity and midgestational pharmacokinetics in mice. Laborde, JB; Roberts, LG; Slikker, W, 1991)	1.72
" Phenytoin elimination was more rapid than was expected, based on previously reported phenytoin pharmacokinetic parameters."	( Pharmacokinetic simulation of the effect of multiple-dose activated charcoal in phenytoin poisoning--report of two pediatric cases. Dolgin, JG; Nix, DE; Sanchez, J; Watson, WA, 1991)	1.42
"We reviewed our data from 122 records of patients taking phenytoin for the treatment of various types of epilepsy and selected 15 (age range 10-43 years old) who were on phenytoin alone to calculate Michaelis-Menten pharmacokinetic parameters."	( Michaelis-Menten pharmacokinetics of phenytoin in adult Malaysian patients. Ismail, R; Rahman, AF, 1990)	0.8
"The developmental toxicity and pharmacokinetic fate of phenytoin in the pregnant rhesus macaque (Macaca mulatta) were examined."	( Developmental toxicity and pharmacokinetics of phenytoin in the rhesus macaque: an interspecies comparison. Binkerd, PE; Hendrickx, AG; Hendrie, TA; Rowland, JR, 1990)	0.78
" It has properties which predispose it to an involvement in pharmacokinetic interactions, a large number of which have been reported."	( Pharmacokinetic drug interactions with phenytoin (Part I). Evans, AM; Milne, RW; Nation, RL, 1990)	0.55
" In addition to physiologic factors, such as blood pressure and cerebral blood flow, pharmacokinetic principles, including half-life, distribution, elimination, and volume of distribution (with special regard to an agent's lipid-solubility rating), should be applied."	( The pharmacokinetics of agents used to treat status epilepticus. Browne, TR, 1990)	0.28
" No difference in the effect on phenytoin pharmacokinetic parameters was noted when the charcoal was administered with or without sorbitol, but fewer gastrointestinal adverse effects were noted without sorbitol treatment."	( The effect of activated charcoal on phenytoin pharmacokinetics. Bertino, JS; Rowden, AM; Spoor, JE, 1990)	0.84
"Oral activated charcoal was shown to affect phenytoin pharmacokinetic parameters."	( The effect of activated charcoal on phenytoin pharmacokinetics. Bertino, JS; Rowden, AM; Spoor, JE, 1990)	0.82
"Routine clinical pharmacokinetic data collected from outpatients receiving phenytoin (PHT) were reanalyzed to estimate population pharmacokinetic parameters."	( Population pharmacokinetics of phenytoin from routine clinical data in Japan: an update. Aoyama, T; Higuchi, S; Yukawa, E, 1990)	0.8
" Because of the long elimination half-life for amiodarone previously reported in healthy volunteers after single doses of amiodarone and the frequent administration of amiodarone associated with this half-life, a modified equation for a continuous infusion was used to describe each subject's ASC versus time data."	( Effect of phenytoin on the clinical pharmacokinetics of amiodarone. Gear, K; Hoyer, GL; Karol, MD; Marcus, FI; Nolan, PE, 1990)	0.68
" No significant differences were observed in the fraction unbound or pharmacokinetic parameters of ACC-9653, phenytoin, or diazepam when ACC-9653 was administered alone compared to concomitant administration with diazepam."	( Evaluation of the pharmacokinetic interaction between diazepam and ACC-9653 (a phenytoin prodrug) in healthy male volunteers. Brouwer, KL; Donn, KH; Dukes, GE; Hak, LJ; Hussey, EK; Krol, TF; Messenheimer, JA, 1990)	0.72
"An equation is derived to estimate mean steady state serum concentration (Css) from trough steady state serum concentration (Cmin) which can be used for drugs with either linear or nonlinear pharmacokinetic properties."	( New pharmacokinetic methods: I. Estimation of mean serum concentration from trough serum concentration. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Szabo, GK, 1990)	0.28
"The pharmacokinetic profile of a newly developed Dilantin 300-mg Kapseal formulation was compared with that of currently marketed Dilantin 100-mg Kapseals in both a 300-mg single-dose bioequivalence study in nine healthy volunteers and a once-daily 300-mg multiple-dose study in 18 patients with seizures."	( Pharmacokinetic profile of a 300-mg extended phenytoin sodium capsule (Dilantin) formulation. Buchanan, RA; Kinkel, AW; Randinitis, EJ, )	0.39
" The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy."	( Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration. Achari, R; Bombassaro, AM; Boucher, BA; Rasmussen, SN; Turlapaty, P; Watridge, CB, 1989)	1.92
"We investigated the influence of the population pharmacokinetic parameters on the performance of the Bayesian feedback method in predicting the phenytoin (PHT) dosage needed to achieve a desired PHT serum concentration."	( Clinical evaluation of population pharmacokinetic parameters in phenytoin dosage adjustment. Aoyama, T; Higuchi, S; Yukawa, E, 1989)	0.72
"A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin."	( Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy. Albani, F; Baruzzi, A; Bianchi, A; Messori, A; Muscas, GC; Riva, R; Valenza, T; Zaccara, G; Zagnoni, P; Zolo, P, )	0.58
"The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 17 epileptic Saudi patients receiving phenytoin."	( Phenytoin Michaelis-Menten pharmacokinetics in Saudi patients. el-Sayed, YM; Islam, SI, 1989)	1.93
"0004); and the apparent elimination half-life increased from 16."	( Pharmacokinetic interaction between intravenous phenytoin and amiodarone in healthy volunteers. Bliss, M; Gear, K; Hoyer, GL; Marcus, FI; Nolan, PE, 1989)	0.53
" To investigate the mechanism of the fall in steady-state plasma phenytoin concentration relative to drug dose that occurs during pregnancy, single dose pharmacokinetic studies with stable isotope labelled phenytoin were carried out at different stages of pregnancy, and 2 to 4 months post-natally, in five epileptic women receiving regular oral therapy with the drug."	( The effect of pregnancy in humans on the pharmacokinetics of stable isotope labelled phenytoin. Dickinson, RG; Eadie, MJ; Hooper, WD; Lander, CM; Wood, B, 1989)	0.74
"Routine clinical pharmacokinetic data collected from out-patients who received phenytoin were analysed to estimate population pharmacokinetic parameters."	( Population pharmacokinetics of phenytoin from routine clinical data in Japan. Aoyama, T; Higuchi, S; Yukawa, E, 1989)	0.79
"The influence of progabide, a new antiepileptic drug, on the pharmacokinetic profiles of phenobarbital, phenytoin, carbamazepine, and valproic acid was evaluated in four separate studies, each including six young healthy volunteers."	( Pharmacokinetic interactions of progabide with other antiepileptic drugs. Bianchetti, G; Morselli, PL; Padovani, P; Thénot, JP; Thiercelin, JF, )	0.35
" Doxorubicin single-dose pharmacokinetic studies were performed in 10 New Zealand White rabbits after pretreatment with phenytoin or phenytoin vehicle (control) infusions in crossover fashion with 4-6 weeks between studies."	( Effect of phenytoin on the pharmacokinetics of doxorubicin and doxorubicinol in the rabbit. Brenner, DE; Cusack, BJ; Loseke, VL; Olson, RD; Tesnohlidek, DA; Vestal, RE, 1988)	0.89
"05) with respect to the area under the plasma phenytoin concentration-time curve, the fraction of phenytoin unbound in plasma, the area under the unbound phenytoin concentration-time curve, the elimination half-life of phenytoin or the fraction of the dose excreted in urine as free and conjugated hydroxyphenylphenylhydantoin."	( Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin. Coulthard, K; Milne, RW; Nation, RL; Penna, AC; Roberts, G; Sansom, LN, 1988)	0.76
"This preliminary clinical study describes the pharmacokinetic characteristics of flunarizine (FLN) following single and multiple dosing in epileptic patients receiving comedication."	( Pharmacokinetic profile of flunarizine after single and multiple dosing in epileptic patients receiving comedication. Barber, K; Cereghino, JJ; Di Giorgio, C; Kapetanovic, IM; Kupferberg, HJ; Lau, M; Norton, L; Torchin, CD; Treiman, DM; Whitley, L, )	0.13
" The prodrug, after achieving a maximum concentration at the end of the 30-minute infusion (Cmax 20, 36, 75, 129 micrograms/mL) declined rapidly with a half-life (t1/2) of about 8 minutes."	( Safety, tolerance and pharmacokinetics of intravenous doses of the phosphate ester of 3-hydroxymethyl-5,5-diphenylhydantoin: a new prodrug of phenytoin. Donn, KH; Gerber, N; Guthrie, RM; Laddu, A; Mays, DC; Quon, CY; Rivenburg, WK; Turlapaty, P, 1988)	0.48
" Compared with control, metronidazole significantly prolonged phenytoin half-life (23 versus 16 hours, P less than ."	( Metronidazole impairs clearance of phenytoin but not of alprazolam or lorazepam. Blyden, GT; Greenblatt, DJ; Scavone, JM, 1988)	0.79
"Disposition of 1-benzenesulfonyl-5,5-diphenylhydantoin (II) having a potent anti-inflammatory activity was compared with that of 5,5-diphenylhydantoin (I), an antiepileptic drug, in order to elucidate whether the pharmacodynamic difference between them can be explained by their physicochemical and pharmacokinetic properties."	( Biopharmaceutical studies on hydantoin derivatives. V. Pharmacokinetics and pharmacodynamics of 5,5-diphenylhydantoin and 1-benzenesulfonyl-5,5-diphenylhydantoin. Fujioka, H; Kishi, M; Masuda, Y; Miyazaki, H; Tan, T; Yokoyama, Y, 1986)	0.27
" Distribution and clearance of isoxicam were probably not affected as its half-life was not changed, its plasma peak concentration increased, and the time to reach this peak decreased."	( The effect of administration of phenytoin on the pharmacokinetics of isoxicam. Caillé, G; Du Souich, P; Lacasse, Y; Larivière, L; Vézina, M, )	0.41
" The peak concentration, and apparent elimination half-life of phenytoin also tended to be increased though not significantly."	( Oral phenytoin pharmacokinetics during omeprazole therapy. Kitchingman, GK; Langman, MJ; Prichard, PJ; Richens, A; Somerville, KW; Walt, RP; Williams, J, 1987)	1.03
" The pharmacokinetic values, dosages, and SSSCs were used for predicting the dosage required to attain an SSSC of 14."	( Comparison of four single-point phenytoin dosage prediction techniques using computer-simulated pharmacokinetic values. Jameson, JP; Toscano, JP, 1986)	0.55
"Stable-isotope tracer methods are described for answering the following questions about a drug: Does the drug exhibit dose-dependent changes in pharmacokinetic properties? What are the drug's Michaelis constant (Km) and maximum velocity (Vmax) for enzymatic biotransformation; Are the dose-dependent pharmacokinetic changes great enough to be clinically important? and Which routes of the drug's biotransformation are responsible for the drug's dose-dependent pharmacokinetic properties? Illustrative data are provided from tracer studies performed with a drug with dose-dependent pharmacokinetic properties, phenytoin, and a drug that does not exhibit dose-dependent pharmacokinetic properties, phenobarbital."	( Pharmacokinetics: dose-dependent changes. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Schumacher, GE; Szabo, GK, )	0.29
"Various pharmacokinetic parameters--disposition half-life, t1/2,z, metabolic clearance CLm, volume of distribution V, intrinsic clearance of unbound drug CLuint, and unbound volume of distribution of tissues (distributive tissue volume/fraction of drug in tissue unbound, VT/fuT--are compared in rat and human for nine weakly acidic drugs, phenytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, and amobarbital, and six weakly basic drugs, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam."	( Prediction of the disposition of nine weakly acidic and six weakly basic drugs in humans from pharmacokinetic parameters in rats. Hanano, M; Iga, T; Sawada, Y; Sugiyama, Y, 1985)	0.44
"05) changes occurred during monotherapy: (1) Apparent (from tracer doses) PHT total clearance by linear method decreased; (2) apparent PHT elimination half-life increased; (3) apparent mean PHT serum concentration per unit dose increased; (4) apparent rate of excretion of p-hydroxyphenyl-phenylhydantoin (p-HPPH) decreased; (5) apparent rate of excretion of PHT dihydrodiol increased; and (6) apparent PHT total clearance and elimination half-life and apparent p-HPPH rate of excretion were dose dependent."	( Studies with stable isotopes I: Changes in phenytoin pharmacokinetics and biotransformation during monotherapy. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Schumacher, GE; Szabo, GK, )	0.39
" Lidocaine pharmacokinetic parameters were unchanged in the presence of amiodarone."	( Effect of amiodarone on the pharmacokinetics of phenytoin, quinidine, and lidocaine in the rat. DiGregorio, GJ; Fruncillo, RJ; Kozin, SH, 1985)	0.52
" Pharmacokinetic interactions between antiepileptic drugs may lead to considerable fluctuation in plasma drug concentration, and monotherapy is often preferable."	( Pharmacokinetics of antiepileptic drugs. Neuvonen, PJ; Tokola, RA, 1983)	0.27
" Depending on its pharmacokinetic parameters, each drug effect has a different onset, intensity, and time course."	( Clinical pharmacokinetics of drugs used in the treatment of status epilepticus. Baars, AM; van der Dries, A; van der Kleijn, E; Vree, TB, 1983)	0.27
" Plasma phenytoin concentration - time data were analysed by three different pharmacokinetic techniques."	( Bioavailability and pharmacokinetics of phenytoin during pregnancy. Chalk, JB; de Wytt, C; Eadie, MJ; Lander, CM; Livingstone, I; Smith, MT; Symoniw, P, 1984)	0.97
"Previously reported routine phenytoin clinical pharmacokinetic data from Japan, England, and Germany were analysed to estimate population pharmacokinetic parameters."	( Steady-state pharmacokinetics of phenytoin from routinely collected patient data. Boenigk, HE; Chiba, K; Dunlop, A; Grasela, TH; Ishizaki, T; Mullen, PW; Rambeck, B; Richens, A; Sheiner, LB; Wadsworth, J, )	0.71
" Oxazepam elimination half-life was shorter and apparent oral clearance higher in treated patients than in age and sex matched control subjects."	( Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Hawksworth, GM; Khir, AS; Petrie, JC; Scott, AK; Steele, WH, 1983)	0.5
"The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 135 epileptic paediatric patients receiving phenytoin as their only anticonvulsant therapy."	( Phenytoin Michaelis-Menten pharmacokinetics in Caucasian paediatric patients. Bauer, LA; Blouin, RA, )	1.78
"Over the past few years, numerous pharmacokinetic techniques based on Michaelis-Menten principles have been proposed to individualize PHT dosage and predict plasma levels."	( Comparative analysis of the pharmacokinetic techniques available for individualizing phenytoin dosage. Arnetoli, G; Bartoli, C; Donati-Cori, G; Messori, A; Muscas, GC; Tendi, E; Valenza, T; Zaccara, G, 1983)	0.49
"The pharmacokinetic parameters controlling paraldehyde elimination were determined in nine infants infused with paraldehyde at the rate of 150 mg/kg/hr in a 5% solution in 5% dextrose for the treatment of status epilepticus."	( Pharmacokinetics of paraldehyde disposition in the neonate. Boutwell, WC; Gessner, PK; Giacoia, GP; Zaleska, MM, 1984)	0.27
"Displacement of one drug by another from blood and/or tissue protein will alter the pharmacokinetic behaviour of the displaced drug."	( Pharmacokinetic consequences of drug displacement from blood and tissue proteins. MacKichan, JJ, 1984)	0.27
" It may be possible to use such information in pharmacokinetic models that incorporate existing knowledge and judgment to predict pharmacokinetics in intact animals including man."	( Species similarities in pharmacokinetics. Bischoff, KB; Dedrick, RL, 1980)	0.26
" The therapeutic dose, clearance, extraction coefficient, bioavailability and half-life are the object of particular study."	( [Pharmacokinetics of anti-arrhythmics. 2. Clinical applications]. Bricaud, H; Lévy, RH; Lévy, S, 1980)	0.26
" This review contains relevant pharmacokinetic data on anticonvulsant drugs widely used during pregnancy and the neonatal period."	( Anticonvulsants during pregnancy and lactation. Transplacental, maternal and neonatal pharmacokinetics. Egger, HJ; Helge, H; Kuhnz, W; Nau, H; Rating, D, )	0.13
" Pharmacokinetic of propranolol, phenytoin and lidocain was studied in groups of male "Fauve de Bourgogne" rabbits."	( [Pharmacokinetics of propranolol, phenytoin and lidocaine in hypercholesterolemic rabbits]. Albin, H; Pehourcq, F; Ploux, D; Vinçon, G, )	0.69
"The relationships between phenytoin dose, pharmacokinetic variables, patient data, and serum phenytoin concentrations were studied."	( Phenytoin dosage requirements and pharmacokinetic variables. Berg, MJ; Ludden, TM; Lyon, LW; Murphy, MJ; Perry, PJ; Taylor, JW, )	1.87
"In the preceding articles, a number of pharmacokinetic concepts have been introduced, and a number of parameters such as plasma half-life, volume of distribution and clearance have been defined."	( Elementary pharmacokinetics in clinical practice. 3: Practical pharmacokinetic applications. Paxton, JW, 1981)	0.26
"The development and implementation of a quality assurance program for a clinical pharmacokinetic service is described."	( Quality assurance program for a clinical pharmacokinetic service. Blouin, RA; Lawson, LA; Parker, PF, 1982)	0.26
" Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole."	( Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin, tumor response and neurotoxicity. Dawes, PJ; Henk, JM; Moore, JL; Paterson, IC, )	0.61
" An understanding of the pharmacokinetic properties of phenytoin greatly facilitates the management of seizure patients."	( Phenytoin: pharmacokinetics and clinical therapeutics. Finn, AL; Olanow, CW, 1981)	1.95
"Individual pharmacokinetic par parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean kinetics, interindividual variability, and residual intraindividual variability plus measurement error."	( Evaluation of methods for estimating population pharmacokinetics parameters. I. Michaelis-Menten model: routine clinical pharmacokinetic data. Beal, SL; Sheiner, LB, 1980)	0.26
"Three programs are presented which have been developed to simulate conditions encountered in the pharmacokinetic adjustment of dosage regimens."	( A package of computer programs designed to simulate pharmacokinetic monitoring of drug therapy. Sullivan, TJ; Wunderley, DJ, 1980)	0.26
"The half-life and metabolic clearance rate (MCR) of antipyrine and phenytoin were determined in 14 young (mean age: 28."	( Disposition of antipyrine and phenytoin correlated with age and liver volume in man. Bach, B; Hansen, JM; Kampmann, JP; Rasmussen, SN; Skovsted, L, )	0.66
"Four methods for estimating dosage regimens for drugs exhibiting non-linear pharmacokinetic behavior (e."	( Using pharmacokinetics in drug therapy. VI: Comparing methods for dealing with nonlinear drugs like phenytoin. Schumacher, GE, 1980)	0.48
" For this and other reasons, at the Hospital Pharmacological Service a clinical pharmacokinetic laboratory was set up about two years ago."	( Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy. Bonora, MR; Guaglio, R; Rondanelli, R; Terzoni, PA, 1980)	0.26
" The simultaneous pharmacokinetic analysis of the plasma levels and urinary excretion data of phenytoin and its major metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, yielded detailed information about the pharmacokinetics of phenytoin."	( Use of stable isotopes in the study of pharmacokinetics of drugs by mass fragmentography II: Detailed examination of pharmacokinetics of a single oral dose of phenytoin in humans. Baba, S; Goromaru, T; Kasuya, Y; Yamazaki, K, 1980)	0.68
"Routine clinical pharmacokinetic data collected from epileptic out-patients who received phenytoin (PHT) were analysed to estimate population pharmacokinetic parameters."	( [NONMEM approach for estimating population pharmacokinetic parameters of phenytoin in Chinese epileptics]. Cai, MH; Chen, G; Chu, XM; Rui, JZ, 1995)	0.74
"The pharmacokinetic variability of moclobemide, a new short half-life reversible selective inhibitor of monoamine oxidase (MAO) was investigated through analysis of concentrations measured during early open clinical use."	( Potential of concentration monitoring data for a short half-life drug: analysis of pharmacokinetic variability for moclobemide. Balant, LP; Balant-Gorgia, AE; Gex-Fabry, M, 1995)	0.29
" Pharmacokinetic assays were performed in all animals after 2 months of the experiment."	( The pharmacokinetics of phenytoin in rabbits with hyperlipidemia induced by high-fat diet. Droździk, M; Gawrońska-Szklarz, B; Wójcicki, J, 1994)	0.6
"The temporal pharmacokinetic (blood) and neuropharmacokinetic (cerebrospinal fluid, CSF) interrelationship of phenytoin was studied after acute and during chronic (up to 5 days) intraperitoneal administration of phenytoin (30, 50 or 100 mg/kg) using a new freely behaving rat model."	( Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: phenytoin. Hjelm, M; Lolin, YI; Patsalos, PN; Ratnaraj, N, 1994)	0.7
" The plasma cyclophosphamide disposition data of these patients were fit by a one-compartment pharmacokinetic model, in which the decline of plasma cyclophosphamide concentration after reaching the initial steady state was modeled as being due to an increase in the clearance rate of cyclophosphamide."	( Nonlinear pharmacokinetics of cyclophosphamide in patients with metastatic breast cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation. Black, KC; Chen, TL; Colvin, OM; Grochow, LB; Kennedy, MJ; Noe, DA; Passos-Coelho, JL, 1995)	0.29
" A review of published studies involving small numbers of elderly subjects or patients given phenytoin sodium, valproic acid, or carbamazepine demonstrates decreased protein binding and intrinsic clearance and increased half-life with advancing age."	( Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Cloyd, JC; Lackner, TE; Leppik, IE, 1994)	0.51
" An understanding of the underlying pharmacokinetic processes, including the need of most elderly patients for lower doses and longer dosing intervals, permits more effective management of therapy and reduces the risk for adverse reactions."	( Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Cloyd, JC; Lackner, TE; Leppik, IE, 1994)	0.29
"The pharmacokinetic interaction between phenytoin and tirilazad was studied in 12 healthy men who received 200 mg phenytoin orally every 8 hours for 11 doses and 100 mg for the remaining 5 doses in one period of a two-way crossover study."	( The effect of phenytoin on the pharmacokinetics of tirilazad mesylate in healthy male volunteers. Fleishaker, JC; Hulst, LK; Peters, GR, 1994)	0.92
" Pharmacokinetic analysis was performed to determine if there were differences between the area under the concentration time curve (AUC), maximum serum concentration, Cmax, and time of maximum serum concentration, Tmax, of phenytoin before and during co-administration of ciprofloxacin."	( Effect of ciprofloxacin on the pharmacokinetics of multiple-dose phenytoin serum concentrations. Arn, SK; D'Souza, MJ; Jacobs, NF; Job, ML; Strom, JG, 1994)	0.71
"We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme."	( Pharmacokinetics of phenytoin in routine clinic patients in Malaysia. Chand, P; Ismail, R; Rahman, AF, 1994)	0.83
" VP-16 concentrations were measured in all plasma samples by high-performance liquid chromatography (HPLC) and electrochemical detection, and the results were analyzed with a pharmacokinetic data analysis system."	( Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies. Bewermeier, P; Hossfeld, DK; Krüger, W; Mross, K; Stockschläder, M; Zander, A, 1994)	0.29
"All calculated pharmacokinetic parameters in the two patient groups (VP-16 administered diluted or undiluted) were similar."	( Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies. Bewermeier, P; Hossfeld, DK; Krüger, W; Mross, K; Stockschläder, M; Zander, A, 1994)	0.29
"The two administration modes for VP-16, either diluted or undiluted, are bioequivalent in pharmacokinetic terms."	( Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies. Bewermeier, P; Hossfeld, DK; Krüger, W; Mross, K; Stockschläder, M; Zander, A, 1994)	0.29
" In this context, anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin (PHT) and valproate (VPA) were assessed in an experimental model in mice."	( Pharmacodynamic interactions between phenytoin and valproate: individual and combined antiepileptic and neurotoxic actions in mice. Bourgeois, BF; Chez, MG; Knowles, WD; Pippenger, CE, 1994)	0.79
" The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group."	( The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat. Tanira, MO; Wasfi, IA, 1993)	0.53
" These results suggest that ZNS has little effect on the pharmacokinetic behaviors of other antiepileptic drugs."	( Pharmacokinetic interaction of zonisamide in rats. Effect of zonisamide on other antiepileptics. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1993)	0.29
" Plasma concentrations of total phenytoin, unbound phenytoin, and the major metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, were measured, and pharmacokinetic variables obtained before and after barbiturate therapy were compared."	( Effect of barbiturate therapy on phenytoin pharmacokinetics. Abe, J; Asada, A; Fujimori, M; Kaji, A; Nishi, S; Oda, Y; Yoshida, N, 1993)	0.85
"Measurement of the absolute bioavailability of phenytoin (PHT) derived from test doses of phenytoin prodrug (PPD) at therapeutic PHT serum concentrations is complicated by two problems: 1) the area under the serum concentration versus time curve (AUC) produced by a given size of test dose will vary directly with background PHT serum concentration due to the nonlinear pharmacokinetic properties of PHT; 2) PPD is more water soluble than PHT, making renal excretion of PPD more likely."	( Bioavailability studies of drugs with nonlinear pharmacokinetics: II. Absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by double-stable isotope technique. Browne, TR; Davoudi, H; Dougherty, CL; Evans, BA; Evans, JE; Kres, J; McEntegart, C; Miceli, JJ; Quon, C; Szabo, GK, 1993)	0.75
" The terminal elimination half-life (t1/2z) is relatively long in neonates; it then decreases during the first postnatal month to lower values than in adults, and then progressively increases with age due to an age-dependent decrease in the metabolic rate."	( Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine and felbamate. Avanzini, G; Battino, D; Estienne, M, 1995)	0.52
" PHT rapidly entered the brain ECF compartment, with Tmax values similar to those of serum."	( Microdialysis study of the neuropharmacokinetics of phenytoin in rat hippocampus and frontal cortex. Alavijeh, MS; Patsalos, PN; Shorvon, SD; Walker, MC, 1996)	0.54
"There were no significant differences between the sertraline group and the placebo group in the pharmacokinetic parameters of phenytoin."	( Absence of effect of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin. Cross, M; Muirhead, DC; Rapeport, WG; Wesnes, K; Williams, SA, 1996)	0.73
" Pharmacokinetic data were analysed utilising noncompartmental and Michaelis-Menten-based population pharmacokinetic analysis."	( Lack of pharmacokinetic interaction between zileuton and phenytoin in humans. Cavanaugh, JH; Granneman, GR; Mukherjee, D; Samara, E, 1995)	0.54
" Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlation coefficient (r) between clearance and body weight was calculated for each drug."	( Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. Ashikari, Y; Chiba, S; Kodama, Y; Kuranari, M; Sakata, T; Takeyama, M, 1996)	0.66
"To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water-soluble phenytoin prodrug, after intramuscular and intravenous administration."	( The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Boucher, BA; Dean, JC; Feler, CA; Kramer, RE; Kugler, AR; Michie, DD; Parks, BR; Smith, KR; Tipton, BK; Young, B, )	0.61
"The potential pharmacokinetic interaction between atovaquone and phenytoin was investigated in 12 healthy male volunteers."	( Atovaquone has no effect on the pharmacokinetics of phenytoin in healthy male volunteers. Davis, JD; Dixon, R; Khan, AZ; Posner, J; Rolan, PE; Toon, S, 1996)	0.78
" These findings suggested that the genetic polymorphism of CYP2C isoenzymes plays an important role in the pharmacokinetic variability of phenytoin, and that the mutation in CYP2C9 proteins is a determinant of impaired metabolism of the drug."	( Effect of CYP2C polymorphisms on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Furusho, K; Hashimoto, Y; Hattori, H; Iui, K; Odani, A; Otsuki, Y; Takano, M, 1996)	0.74
"The population pharmacokinetic parameters of phenytoin were estimated using routine therapeutic drug monitoring data from 116 epileptic patients."	( Population pharmacokinetics of phenytoin in Japanese patients with epilepsy: analysis with a dose-dependent clearance model. Furusho, K; Hashimoto, Y; Hattori, H; Inui, K; Koue, T; Odani, A; Otsuki, Y; Takano, M; Takayanagi, K; Yasuhara, M, 1996)	0.84
" The subjects received a single oral dose of phenytoin, 300 mg, on day 1 of the study and the pharmacokinetic profile of the drug was determined."	( The effect of nefazodone on the single-dose pharmacokinetics of phenytoin in healthy male subjects. Hammett, JL; Langenbacher, KM; Marino, MR; Nichola, P; Uderman, HD, 1997)	0.8
" Although statistically significant, the changes in the pharmacokinetic parameters of phenytoin and unbound phenytoin were small."	( Evaluation of pharmacokinetic interaction between bromfenac and phenytoin in healthy males. Cevallos, WH; DeCleene, SA; Gumbhir-Shah, K; Korth-Bradley, JM, 1997)	0.76
"The effects of the macrolide antibiotics, erythromycin, clarithromycin and roxithromycin, on the pharmacokinetic profile of phenytoin were studied in rats."	( Pharmacokinetic interactions between erythromycin, clarithromycin, roxithromycin and phenytoin in the rat. al-Humayyd, MS, )	0.56
" The equations describing the models for AUC using two time points (3 and 24h) and Cmax for the training data set of 30 subjects were AUCpredicted = 11."	( A limited sampling method for the estimation of flunarizine area under the curve (AUC) and maximum plasma concentration (Cmax). Mahmood, I; Sahlroot, JT, 1997)	0.3
" No clinically relevant pharmacokinetic interactions were noted between felbamate and lamotrigine, clonazepam, vigabatrin, nor the active monohydroxy metabolite of oxcarbazepine."	( Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation. Banfield, CR; Glue, P; Levy, RH; Mather, GG; Perhach, JL; Racha, JK, 1997)	0.3
" The pharmacokinetic parameters of phenytoin in individual patients were estimated by means of empirical bayesian analysis, in which the prior information was the population parameters for Japanese patients with epilepsy."	( Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Furusho, K; Hashimoto, Y; Hattori, H; Inui, K; Odani, A; Otsuki, Y; Uwai, Y, 1997)	0.8
"The findings indicated that the genetic polymorphisms of CYP2C isozymes play an important role in the pharmacokinetic variability of phenytoin and that the mutation in CYP2C9 proteins (Ile359-->Leu) is a determinant of impaired metabolism of the drug among Japanese persons."	( Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Furusho, K; Hashimoto, Y; Hattori, H; Inui, K; Odani, A; Otsuki, Y; Uwai, Y, 1997)	0.72
"To conduct a population pharmacokinetic analysis of carbamazepine (CBZ)."	( Population pharmacokinetics of carbamazepine in adults with epilepsy. Ahman, P; Brundage, RC; Cascino, G; Graves, NM; Krause, S; Leppik, IE; Rarick, J; So, E; Wen, Y, )	0.13
" Pharmacokinetic data and occurrence of AE were compared between the two groups at the time of the single-dose kinetic study, at the completion of the switchover to CBZ, and 4 weeks after discontinuation of the previous AED."	( Rapid switchover to carbamazepine using pharmacokinetic parameters. Bourgeois, BF; Hasegawa, H; Hutson, P; Kanner, AM, 1998)	0.3
"To study the benefits of a clinical pharmacokinetic service in optimising phenytoin use in the Western Cape."	( Benefits of a clinical pharmacokinetic service in optimising phenytoin use in the western Cape. Folb, PI; Kies, BM; Seymour, MA; Valodia, P, 1998)	0.77
"The clinical pharmacokinetic dosing service for phenytoin applied in this study contributed significantly to the success of epilepsy management."	( Benefits of a clinical pharmacokinetic service in optimising phenytoin use in the western Cape. Folb, PI; Kies, BM; Seymour, MA; Valodia, P, 1998)	0.8
" Additional pharmacokinetic investigations are recommended to optimise pharmacological outcomes in patients with severe head injury."	( Pharmacokinetic alterations after severe head injury. Clinical relevance. Boucher, BA; Hanes, SD, 1998)	0.3
"Stable isotope analogues of phenytoin are useful for pulse dose pharmacokinetic studies in epilepsy patients."	( A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies. Birnbaum, AK; Nelson, MH; Nyhus, PJ; Remmel, RP, 1998)	0.86
"Enzymatic biotransformation is the principal determinant of the pharmacokinetic properties of most antiepileptic drugs (AEDs), although some agents are excreted by the kidneys predominantly as unchanged drug."	( Pharmacokinetics of antiepileptic drugs. Browne, TR, 1998)	0.3
" It is concluded that the synergism may be due to a pharmacodynamic rather than a pharmacokinetic interaction."	( Pharmacodynamic interaction between phenytoin and sodium valproate changes seizure thresholds and pattern. Danhof, M; Della Paschoa, OE; Hamstra, R; Kruk, MR; Voskuyl, RA, 1998)	0.58
" In addition, a population pharmacokinetic analysis was performed."	( The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Higuchi, S; Ieiri, I; Imai, J; Mamiya, K; Ninomiya, H; Otsubo, K; Shimamoto, J; Tashiro, N; Yamada, H; Yukawa, E, 1998)	0.54
" A population pharmacokinetic analysis (NONMEM analysis) was performed to evaluate whether genetic polymorphism of CYP2C9/19 affects the clinical use of PHT by using the 336 dose-serum concentration data."	( The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Higuchi, S; Ieiri, I; Imai, J; Mamiya, K; Ninomiya, H; Otsubo, K; Shimamoto, J; Tashiro, N; Yamada, H; Yukawa, E, 1998)	0.54
" PHT pharmacokinetics was described by a pharmacokinetic model with Michaelis-Menten elimination."	( Modelling of the pharmacodynamic interaction between phenytoin and sodium valproate. Danhof, M; Della Paschoa, OE; Voskuyl, RA, 1998)	0.55
"The influence of various covariates (including weight, race, smoking, gender, age, mild-to-moderate alcohol intake, and body surface area) on the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa was investigated."	( Factors influencing the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa. Folb, PI; McFadyen, ML; Miller, R; Seymour, MA; Valodia, P, 1999)	0.73
"03 microg h mL(-1)), the elimination half-life was also significantly (P<0."	( Pharmacokinetic interaction in rabbits between a new anticonvulsant, DL-3-hydroxy-3-ethyl-3-phenylpropionamide, and phenytoin. Fernández, A; García, L; Jung, H; Medina, L; Pérez, R, 1998)	0.51
" The pharmacokinetic assessment was repeated on day 18."	( Lack of pharmacokinetic drug interactions between tiagabine and carbamazepine or phenytoin. Boellner, SW; Cao, GX; Cato, A; Guenther, HJ; Gustavson, LE; Qian, JX; Sommerville, KW, 1998)	0.53
"Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines."	( Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. Chen, C; Cox, E; Fiedler-Kelly, J; Grasela, TH; Risner, ME; Womble, GP, 1999)	0.3
" Pharmacokinetic analysis revealed significant decrease in steady state maximum concentration (Cmax), through concentration (Cmin), elimination half life (t 1/2 e) and the area under plasma time concentration curve (AUC0-24) of phenytoin when co-administered with ciprofloxacin."	( Effect of ciprofloxacin on steady state pharmacokinetics of phenytoin in rabbits. Bhargava, VK; Garg, SK; Islam, AF, 1999)	0.73
"The pharmacokinetic behavior of fosphenytoin (FOS), the water-soluble prodrug of phenytoin (PHT), has been characterized in normal subjects."	( Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease. Alldredge, BK; Aweeka, FT; Boyer, TD; Eldon, MA; Gambertoglio, JG; Gottwald, MD; Kugler, AR; Pollock, AS; Wright, TL, 1999)	0.89
" Serial plasma concentrations were measured, and pharmacokinetic parameters were calculated."	( Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease. Alldredge, BK; Aweeka, FT; Boyer, TD; Eldon, MA; Gambertoglio, JG; Gottwald, MD; Kugler, AR; Pollock, AS; Wright, TL, 1999)	0.61
"Although the differences in pharmacokinetic parameters between the three groups were not statistically significant, these data suggest the need for close clinical monitoring during FOS administration to patients with hepatic or renal disease."	( Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease. Alldredge, BK; Aweeka, FT; Boyer, TD; Eldon, MA; Gambertoglio, JG; Gottwald, MD; Kugler, AR; Pollock, AS; Wright, TL, 1999)	0.61
" This crossover study was carried out in rhesus monkeys to determine if any pharmacokinetic interaction was involved in such a potentiation."	( Effect of nimodipine, a dihydropyridine calcium channel antagonist, on the steady state pharmacokinetics of phenytoin (DPH) in rhesus monkeys. Garg, SK; Gupta, MC, )	0.34
"This open-label study investigated the pharmacokinetic interaction of phenytoin (PHT) and felbamate (FBM)."	( Coadministration of phenytoin and felbamate: evidence of additional phenytoin dose-reduction requirements based on pharmacokinetics and tolerability with increasing doses of felbamate. Lyness, WH; Perhach, JL; Rosenberg, A; Sachdeo, R; Sachdeo, S; Shumaker, RC; Wagner, ML; Ward, D, 1999)	0.86
" PHT Cmax increased from 15."	( Coadministration of phenytoin and felbamate: evidence of additional phenytoin dose-reduction requirements based on pharmacokinetics and tolerability with increasing doses of felbamate. Lyness, WH; Perhach, JL; Rosenberg, A; Sachdeo, R; Sachdeo, S; Shumaker, RC; Wagner, ML; Ward, D, 1999)	0.63
" There were no statistically significant differences between the two regimens for mean phenytoin Cmax or tmax."	( Lack of pharmacokinetic interaction between lansoprazole and intravenously administered phenytoin. Cavanaugh, JH; Karol, MD; Locke, CS, 1999)	0.75
"004), the elimination half-life was 35% shorter (12."	( Cytochrome P450-inducing antiepileptics increase the clearance of vincristine in patients with brain tumors. Joensuu, H; Kivistö, KT; Mäenpää, H; Neuvonen, PJ; Villikka, K, 1999)	0.3
" No significant difference was observed in any of the pharmacokinetic parameters like Cmax, Cmin, Tmax, t1/2a, t1/2e and AUC of DPH after GFJ administration as compared to control values in healthy volunteers and epileptic patients."	( Lack of pharmacokinetic interaction between grapefruit juice and phenytoin in healthy male volunteers and epileptic patients. Garg, SK; Kumar, N; Prabhakar, S, 1999)	0.54
" Pharmacokinetic data correlated well with pregnancy outcome data."	( Pharmacokinetic data support pharmacologically induced embryonic dysrhythmia as explanation to Fetal Hydantoin Syndrome in rats. Azarbayjani, F; Danielsson, B; Ohman, I; Sköld, AC; Webster, W, 2000)	0.31
" All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype."	( CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics. Hadama, A; Higuchi, S; Ieiri, I; Mamiya, K; Ninomiya, H; Otsubo, K; Tashiro, N; Yukawa, E, )	0.13
" The validity of the pharmacokinetic models and the estimated population parameter values was tested using the naive prediction method."	( Validation of population pharmacokinetic parameters of phenytoin using the parallel Michaelis-Menten and first-order elimination model. Folb, PI; McFadyen, ML; Miller, R; Seymour, MA; Valodia, PN, 2000)	0.55
" The objective of this study was to determine the presence or absence of a pharmacokinetic drug interaction of levetiracetam with phenytoin."	( Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined by new technique. Baltes, E; Browne, TR; Jensen, CM; Josephs, E; Leppik, IE; Paz, J; Szabo, GK, 2000)	0.75
" Plasma concentration curves and pharmacokinetic parameters did not show remarkable differences between the dose groups, indicating that absorption is the limiting factor at the dose range used."	( Comparison of in vitro and in vivo developmental toxicity and pharmacokinetics of phenytoin in the rat. Beekhuijzen, ME; Klaassen, R; Piersma, AH; Rompelberg, CJ; Verhoef, A, 2000)	0.53
" Orally administered GBP did not significantly alter the pharmacokinetic parameters of parenteral PT."	( Effect of vigabatrin and gabapentin on phenytoin pharmacokinetics in the dog. Al-Hassan, MI; Bawazir, SA; Matar, KM; Nicholls, PJ; Tekle, A, 2000)	0.58
" Twenty-four hours after LPS injection, the pharmacokinetic parameters of the four drugs were obtained following intravenous administrations of antipyrine (7 mg/kg), theophylline (5 mg/kg), phenytoin (10 mg/kg) and nifedipine (1 mg/kg)."	( The impact of acute phase response on the plasma clearance of antipyrine, theophylline, phenytoin and nifedipine in rabbits. Kokue, E; Saitoh, T; Shimoda, M, 2000)	0.72
" Time-invariant and time-variant Michaelis-Menten pharmacokinetic models were fit to the unbound phenytoin concentration-time data (ADAPT II)."	( Altered phenytoin pharmacokinetics in children with severe, acute traumatic brain injury. Lee, KR; Phelps, SJ; Storgion, SA; Stowe, CD, 2000)	0.96
" All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration."	( Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses. DeToledo, J; Gidal, B; Morgan, RO; Pryor, FM; Ramsay, RE, 2001)	0.93
" Pharmacokinetic parameters during and after mild therapeutic hypothermia were compared."	( Effect of mild therapeutic hypothermia on phenytoin pharmacokinetics. Asada, A; Iida, Y; Nishi, S, 2001)	0.57
" Orally administered GBP did not significantly alter the pharmacokinetic parameters of parental PT."	( Effect of vigabatrin and gabapentin on phynytoin pharmacokinetics in the dog. al-Hassan, MI; Bawazir, SA; Matar, KM; Nicholls, PJ; Tekle, A, )	0.13
"In the present study, Mentat, a herbomineral psychotropic preparation, was studied for its pharmacokinetic interaction with the commonly used anti-epileptic drugs, carbamazepine and phenytoin."	( Pharmacokinetic interactions of Mentat with carbamazepine and phenytoin. Gopumadhavan, S; Mitra, SK; Rafiq, M; Sundaram, R; Tripathi, M; Venkataranganna, MV, )	0.56
" However, there are far fewer reports about the pharmacokinetic interactions between PHT and traditional Chinese medicines (TCMs)."	( Effects of Paeoniae Radix, a traditional Chinese medicine, on the pharmacokinetics of phenytoin. Chen, LC; Chou, MH; Lin, MF; Yang, LL, 2001)	0.53
" The plasma concentrations were used to construct pharmacokinetic profiles by plotting drug concentration-time curves."	( Effects of Paeoniae Radix, a traditional Chinese medicine, on the pharmacokinetics of phenytoin. Chen, LC; Chou, MH; Lin, MF; Yang, LL, 2001)	0.53
"The significant increase in Tmax indicated that simultaneous oral administration of PR delayed the absorption of PHT."	( Effects of Paeoniae Radix, a traditional Chinese medicine, on the pharmacokinetics of phenytoin. Chen, LC; Chou, MH; Lin, MF; Yang, LL, 2001)	0.53
" Pharmacokinetic variables were derived from plasma samples collected before and after administration of vecuronium."	( Pharmacokinetics and pharmacodynamics of vecuronium in children receiving phenytoin or carbamazepine for chronic anticonvulsant therapy. Greenblatt, DJ; Martyn, JA; Soriano, SG; Sullivan, LJ; Venkatakrishnan, K, 2001)	0.54
"We compared predicted phenytoin serum concentrations using three Michaelis-Menten pharmacokinetic dosing methods with actual concentrations obtained from physician dosing in an outpatient neurology practice."	( Three Michaelis-Menten pharmacokinetic dosing methods compared with physician dosing of phenytoin in an outpatient neurology practice. Akbari, S; Cobb, HH; Spruill, WJ; Wade, WE, 2001)	0.85
" A preliminary pharmacokinetic study was carried out in mice by administering phenytoin (10 mg) orally, with or without piperine (0."	( Piperine in food: interference in the pharmacokinetics of phenytoin. Bhardwaj, RK; Gupta, SK; Jaiswal, J; Jasuja, R; Velpandian, T, )	0.6
" The pharmacokinetic parameters were analyzed by analysis of variance followed by the Tukey-Kramer test."	( Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis. Dreossi, SA; Garcia, FS; Lanchote, VL; Takayanagui, OM, 2002)	0.31
"To evaluate the potential pharmacokinetic interactions between topiramate (TPM) and phenytoin (PHT) in patients with epilepsy by studying their pharmacokinetics (PK) after monotherapy and concomitant TPM/PHT treatment."	( Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Bialer, M; Bishop, FE; Curtin, CR; Doose, DR; Gisclon, LG; Kunze, KL; Levy, RH; Mather, GG; Roskos, LK; Sachdeo, RC; Sachdeo, SK; Shen, DD; Streeter, AJ; Thummel, KE; Trager, WF, 2002)	0.89
" The half-life for conversion of fosphenytoin to phenytoin ranges from 7-15 minutes."	( Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. Fischer, JH; Fischer, PA; Patel, TV, 2003)	1.22
" dose of fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria."	( Phenytoin pharmacokinetics and clinical effects in African children following fosphenytoin and chloramphenicol coadministration. Kokwaro, GO; Muchohi, SN; Newton, CR; Ogutu, BR; Otieno, GO, 2002)	2.14
" Plasma was separated and assayed for phenytoin using the HPLC technique and various pharmacokinetic parameters were calculated."	( Influence of honey on the pharmacokinetics of phenytoin in healthy rabbits. Garg, SK, 2003)	0.85
" The present studies investigated the pharmacokinetic interactions of voriconazole and phenytoin when coadministered."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	0.81
" Cmax and AUCtau were compared at days 7, 21, and 28 (Study A), and at days 7 and 17 (Study B)."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	0.59
" For subjects receiving voriconazole (200 mg twice daily) plus phenytoin, the day 21/day 7 ratios for voriconazole Cmax and AUCtau were 60."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	0.83
"Repeat dose administration of phenytoin decreased the mean steady-state Cmax and AUCtau of voriconazole by approximately 50% and 70%, respectively."	( Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Eve, MD; Fielding, A; Ghahramani, P; Love, ER; Purkins, L; Wood, N, 2003)	0.88
" Plasma was separated and assayed for phenytoin by high performance liquid chromatography (HPLC) and various pharmacokinetic parameters were calculated."	( Influence of an acidic beverage (Coca-Cola) on the pharmacokinetics of phenytoin in healthy rabbits. Garg, SK; Kondal, A, 2003)	0.82
" Pharmacokinetic and pharmacodynamic modeling was used to characterize the disposition of vecuronium and patient responses to it in the two groups."	( Influence of chronic phenytoin administration on the pharmacokinetics and pharmacodynamics of vecuronium. Caldwell, JE; McCarthy, G; Sharma, ML; Szenohradszky, J; Wright, PM, 2004)	0.64
"To develop a population pharmacokinetic model to evaluate the effects of variety of covariates on clearance of carbamazepine (CBZ) and its main metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese population."	( Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data. Jiao, Z; Shi, XJ; Zhao, ZG; Zhong, MK, 2004)	0.32
" Three pharmacokinetic profiles were performed: on days -7 and -1, to assess pharmacokinetic parameters of oral phenytoin administered alone, and on day 35, after 14 days of zonisamide treatment, to evaluate the effect of zonisamide on phenytoin pharmacokinetics and to characterize zonisamide pharmacokinetics in the presence of phenytoin."	( Lack of a clinically significant effect of zonisamide on phenytoin steady-state pharmacokinetics in patients with epilepsy. Garnett, WR; Levy, RH; Pan, WJ; Ragueneau-Majlessi, I; Rosenfeld, W; Schmerler, M; Shah, J, 2004)	0.78
" Both the steady-state volume of distribution (782 L) and the terminal elimination half-life (17."	( The pharmacokinetics of piritramide after prolonged administration to intensive care patients. Bouillon, T; Groeger, P; Kietzmann, D, 2004)	0.32
"Despite increasing terminal elimination half-life and volume of distribution at steady state (increasing drug load for a given plasma concentration), the context-sensitive half-time of piritramide after 3 days of administration is lower than predicted from bolus kinetics, making the drug a suitable candidate for intensive care unit analgesia."	( The pharmacokinetics of piritramide after prolonged administration to intensive care patients. Bouillon, T; Groeger, P; Kietzmann, D, 2004)	0.32
" Plasma was separated and stored at -20 degrees C until assayed for phenytoin and carbamazepine by HPLC and different pharmacokinetic parameters were calculated."	( Influence of high fat diet (butter) on pharmacokinetics of phenytoin and carbamazepine. Garg, SK; Malhotra, S; Sidhu, S, 2004)	0.8
" The pooled data were analyzed using population pharmacokinetic (POP-PK) methods."	( Population pharmacokinetics of motexafin gadolinium in adults with brain metastases or glioblastoma multiforme. Boswell, GW; Ford, JM; Hutcheson, SJ; Miles, DR; Phan, SC; Renschler, MF; Smith, JA, 2005)	0.33
"Serum concentrations of free-phenytoin (F-PHT) obtained in adult epileptic patients receiving PHT in monotherapy were analyzed to estimate the Michaelis-Menten pharmacokinetic parameters."	( Estimation of population pharmacokinetic parameters of free-phenytoin in adult epileptic patients. Aarons, L; Ahmed, IA; Deleu, D, )	0.66
"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
" Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone."	( Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Alvey, CW; Bockbrader, HN; Brodie, MJ; Bron, NJ; Gibson, GL; Hounslow, NJ; Posvar, EL; Randinitis, EJ; Wesche, DL; Wilson, EA, 2005)	0.55
" Here we present a unique, generic, physiologically based pharmacokinetic (PBPK) model and demonstrate its application to the estimation of rat plasma pharmacokinetics, following intravenous dosing, from in vitro data alone."	( Application of a generic physiologically based pharmacokinetic model to the estimation of xenobiotic levels in rat plasma. Brightman, FA; Leahy, DE; Searle, GE; Thomas, S, 2006)	0.33
" Plasma phenytoin levels were assayed by HPLC, and pharmacokinetic parameters were calculated."	( Effects of artemisinin, artemether, and arteether on the pharmacokinetics of phenytoin. Medhi, B; Pandhi, P; Sukhija, M, 2006)	1
" The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test."	( Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy. Hota, D; Kharbanda, P; Pandhi, P; Pattanaik, S; Prabhakar, S, 2006)	0.58
"These findings indicated that the genetic polymorphisms of CYP2C19 contribute to the pharmacokinetic variability of phenytoin and phenobarbital, the poor metabolizers of CYP2C19, which are relatively common in Asian groups."	( Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and phenobarbital in Japanese epileptic patients using Non-linear Mixed Effects Model approach. Mamiya, K; Yukawa, E, 2006)	0.78
"Phenytoin dosing is critical in cancer patients as to decreased absorption secondary to chemotherapy-induced gastrointestinal toxicity, increased phenytoin metabolism in the liver secondary to chemotherapy, extreme patient profile that falls outside the predicted pharmacokinetic population, frequent hypoalbuminaemia and polydrug treatment."	( Interactions of serum albumin, valproic acid and carbamazepine with the pharmacokinetics of phenytoin in cancer patients. Beijnen, JH; Boogerd, W; Huitema, AD; Joerger, M; Schellens, JH; van der Sande, JJ, 2006)	2
" The pharmacokinetics of the 260 PB concentrations at a steady-state obtained from 79 patients was described with a one-compartment open pharmacokinetic model with first-order elimination."	( Population estimation of the effects of cytochrome P450 2C9 and 2C19 polymorphisms on phenobarbital clearance in Japanese. Goto, S; Ishitsu, T; Murata, T; Nakada, N; Nakagawa, K; Seo, T; Ueda, N, 2007)	0.34
" The elimination half-life for the entire patient population was approximately twofold longer than the value reported in the product labeling (40-50 h vs 22 h)."	( Factors affecting antiepileptic drug pharmacokinetics in community-dwelling elderly. Birnbaum, AK; Cloyd, JC; Marino, S, 2007)	0.34
" Eighteen patients had pharmacokinetic assays of Paclitaxel levels."	( Fractionated stereotactic radiotherapy boost and weekly paclitaxel in malignant gliomas clinical and pharmacokinetics results. Ashamalla, H; Colella, F; Dosik, D; Guriguis, A; Krishnamurthy, M; Lavaf, A; Lewis, L; Mokhtar, B; Nasr, H; Saad, N; Zaki, B, 2007)	0.34
" Because it was known from the literature that the half-life of midazolam can increase at high dosage, the kinetics of midazolam (MDZ), 1'-hydroxymidazolam, and 4-hydroxymidazolam were assessed at steady state (dosage 1 mg/min) and after stopping treatment."	( Pharmacokinetics of midazolam and metabolites in a patient with refractory status epilepticus treated with extraordinary doses of midazolam. Bodmer, M; Grignaschi, N; Haschke, M; Krähenbühl, S; Kummer, O; Link, B; Ruegg, S, 2008)	0.35
" There were no significant differences in any celecoxib pharmacokinetic parameters between 15 +EIASD and 12 -EIASD patients."	( Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma. Batchelor, T; Desideri, S; Grossman, SA; Hammour, T; Lesser, G; Olson, J; Peereboom, D; Supko, JG; Ye, X, 2008)	0.75
" Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated."	( Effects of etoricoxib on the pharmacokinetics of phenytoin. Bansal, V; Gaikwad, S; Medhi, B; Pandhi, P; Prakash, A; Sukhija, M, )	0.82
" The mean elimination half-life was 40 hours."	( Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy. Ahn, JE; Birnbaum, AK; Brundage, RC; Cloyd, JC; Conway, JM; Leppik, IE; Marino, SE; Musib, LC; Ramsay, RE; Rarick, JO; White, JR, 2008)	1.79
" The prolonged elimination half-life suggests that most patients can take PHT once daily and the time to reach steady-state may extend to 2-3 weeks."	( Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy. Ahn, JE; Birnbaum, AK; Brundage, RC; Cloyd, JC; Conway, JM; Leppik, IE; Marino, SE; Musib, LC; Ramsay, RE; Rarick, JO; White, JR, 2008)	1.79
" Because of the alteration in these variables, wide intraindividual variation of pharmacokinetic parameters occurs depending upon the time since thermal injury and fluid resuscitation."	( Influence of burns on pharmacokinetics and pharmacodynamics of drugs used in the care of burn patients. Blanchet, B; Jullien, V; Tod, M; Vinsonneau, C, 2008)	0.35
" As pharmacokinetic studies in this population are hampered by limitations in the number and volume of plasma samples, we developed an LC-MS/MS assay for the simultaneous determination of these medications in small volume human plasma specimens for pharmacokinetic evaluations in neonates."	( A tandem mass spectrometry assay for the simultaneous determination of acetaminophen, caffeine, phenytoin, ranitidine, and theophylline in small volume pediatric plasma specimens. Budha, NR; Christensen, ML; Mehrotra, N; Meibohm, B; Zhang, Y, 2008)	0.56
"African green monkeys (vervets) have been proposed as an alternate species that might allow improved access and provide high-quality pharmacokinetic results comparable with other primates."	( Exploration of the African green monkey as a preclinical pharmacokinetic model: oral pharmacokinetic parameters and drug-drug interactions. Bhadresa, S; Coon, DJ; Lawrence, MS; Magiera, D; Struharik, M; Ward, KW, 2009)	0.35
"liver) was calculated from pharmacokinetic studies and compared to the time-averaged liver intrinsic clearance (CLint."	( Assessment of inter-individual variability in predicted phenytoin clearance. Doogue, MP; Miners, JO; Polak, S; Polasek, TM; Rostami-Hodjegan, A, 2009)	0.6
"Simulations of PHT clearance were most accurate when based on ‘albumin-adjusted’ in vitro kinetic data, and they identified inter-individual variability outside the reported range of pharmacokinetic studies in healthy volunteers (CLint."	( Assessment of inter-individual variability in predicted phenytoin clearance. Doogue, MP; Miners, JO; Polak, S; Polasek, TM; Rostami-Hodjegan, A, 2009)	0.6
"Mechanistic modelling and simulation allow inter-individual variability in clearance to be considered during in vitro–in vivo extrapolation, and this approach may offer a superior indication of variability and covariates in the clinic than that provided by small pharmacokinetic studies."	( Assessment of inter-individual variability in predicted phenytoin clearance. Doogue, MP; Miners, JO; Polak, S; Polasek, TM; Rostami-Hodjegan, A, 2009)	0.6
" The purpose of this study is to investigate conditions for equivalence between M-M and TMDD pharmacokinetic models and provide guidelines for selection between these two approaches."	( Selection between Michaelis-Menten and target-mediated drug disposition pharmacokinetic models. Krzyzanski, W; Mager, DE; Yan, X, 2010)	0.36
" Pharmacokinetic (PK) data were compared with those previously collected in patients (n=127) treated with phenytoin for seizure prophylaxis."	( Influence on Busilvex pharmacokinetics of clonazepam compared to previous phenytoin historical data. Bacigalupo, A; Buzyn, A; Cahn, JY; Carreras, E; Kröger, N; Puozzo, C; Sanz, G; Vernant, JP, 2010)	0.81
"As a consequence of a continuous demand for increased throughput of pharmacokinetic (PK) studies, industries have introduced strategies to reduce the number of samples such as cassette analysis (pooling of samples after the in-life phase)."	( High-throughput analysis of standardized pharmacokinetic studies in the rat using sample pooling and UPLC-MS/MS. Betnér, I; Briem, S; Bueters, T; Dahlström, J; Kvalvågnaes, K, 2011)	0.37
" Serial pharmacokinetic sampling of atorvastatin was conducted on day 7 of atorvastatin dosing and day 70 of lamotrigine + atorvastatin dosing or day 28 of phenytoin + atorvastatin dosing."	( Effects of lamotrigine and phenytoin on the pharmacokinetics of atorvastatin in healthy volunteers. Alexander, S; Bullman, J; Fleck, R; Messenheimer, J; Miller, J; Nicholls, A; Van Landingham, K; Vuong, A, 2011)	0.86
" Incorporation of the relevant physiological and biochemical changes into predictive bottom-up pharmacokinetic models in order to optimize dosage regimens may offer a logical way forward for the cases where no clinical data exist."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
"Extension of a mechanistic predictive pharmacokinetic model to accommodate physiological and biochemical changes associated with obesity and morbid obesity allowed prediction of changes in drug clearance on the basis of in vitro data, with reasonable accuracy across a range of compounds that are metabolized by different enzymes."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
" A population pharmacokinetic model was developed using NONMEM."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
" In population pharmacokinetic modeling, the apparent clearance of OHC was higher by 31."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
" Population pharmacokinetic analysis showed that the apparent clearance of OHC increased with comedication with EIAEDs."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
" Phenytoin plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (C(max)), time to C(max) (t(max)) and half-life (t(1/2)) were estimated by noncompartmental analysis using PK Solutions® software."	( Genetic polymorphism of NAT2 metabolizing enzymes on phenytoin pharmacokinetics in Indian epileptic patients developing toxicity. Jain, DC; Madhuri, B; Manjari, T; Murali, M; Raghavan, S; Vivekanandhan, S, 2012)	1.54
" Pharmacokinetic parameters for phenytoin in toxicity group of poor metabolizers showed a longer elimination half-life of a drug (t(1/2) = 35."	( Genetic polymorphism of NAT2 metabolizing enzymes on phenytoin pharmacokinetics in Indian epileptic patients developing toxicity. Jain, DC; Madhuri, B; Manjari, T; Murali, M; Raghavan, S; Vivekanandhan, S, 2012)	0.91
" The aims of this study were to determine the pharmacokinetic parameters and their variability of carbamazepine in elderly patients and to quantify the effect of covariates on these parameters."	( Population pharmacokinetics of carbamazepine in elderly patients. Birnbaum, AK; Brundage, RC; Collins, JF; Macias, FM; Punyawudho, B; Ramsay, ER, 2012)	0.38
"Prospectively collected carbamazepine concentrations from 121 patients aged 60 years or older were used to develop a population pharmacokinetic model."	( Population pharmacokinetics of carbamazepine in elderly patients. Birnbaum, AK; Brundage, RC; Collins, JF; Macias, FM; Punyawudho, B; Ramsay, ER, 2012)	0.38
" Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated."	( Effect of aceclofenac on pharmacokinetic of phenytoin. Attrey, SD; Bansal, YS; Joshi, R; Medhi, B; Pandhi, P; Prakash, A; Singh, D, 2012)	1.07
"The study objective was evaluation of the pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects."	( Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects. Leucuta, SE; Muntean, D; Neag, M; Popa, A; Vlase, L, 2012)	0.85
" Pharmacokinetic parameters of ivabradine administered in each treatment were calculated using non-compartmental analysis and compared to determine if the differences were statistically significant."	( Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects. Leucuta, SE; Muntean, D; Neag, M; Popa, A; Vlase, L, 2012)	0.63
" Statistically significant differences were observed for the C(max) and AUC(∞) of ivabradine when administered alone or with phenytoin, whereas for t(max) and the half-life the differences were non-significant."	( Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects. Leucuta, SE; Muntean, D; Neag, M; Popa, A; Vlase, L, 2012)	0.84
"We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range."	( Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers. Kasai, H; Kumagai, Y; Shimasaki, S; Shimizu, K; Tanaka, J, 2013)	0.92
" The population pharmacokinetic analysis was performed using NONMEM software."	( Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers. Kasai, H; Kumagai, Y; Shimasaki, S; Shimizu, K; Tanaka, J, 2013)	0.68
" Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight."	( Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers. Kasai, H; Kumagai, Y; Shimasaki, S; Shimizu, K; Tanaka, J, 2013)	0.96
"A population pharmacokinetic model for phenytoin in Asian pediatric patients was developed to determine the influence of concurrent medications, patient demographics, and blood biochemistry on the pharmacokinetic profile of phenytoin."	( Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug. Chan, DW; Chan, E; Ho, PC; Kong, ST; Lee, FX; Tan, WW, 2013)	0.91
"Retrospective clinical data were obtained from 66 patients (age, 1-16 years) for the determination of pharmacokinetic parameters of phenytoin using WinNonmix."	( Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug. Chan, DW; Chan, E; Ho, PC; Kong, ST; Lee, FX; Tan, WW, 2013)	0.84
" Based on the population pharmacokinetic parameters, a nomogram was subsequently developed for dose individualization of phenytoin in Asian pediatric patients."	( Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug. Chan, DW; Chan, E; Ho, PC; Kong, ST; Lee, FX; Tan, WW, 2013)	0.85
" Phenytoin was given orally at a dose of 50 mg, and blood samples were obtained for the determination of drug's pharmacokinetic parameters."	( Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin pharmacokinetics in beagle dogs. Ahmad, A; Al-Jenoobi, FI; Al-Mohizea, AM; Al-Suwayeh, SA; Alkharfy, KM; Khan, RM, 2013)	1.53
" Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated."	( Effect of esomeprazole on pharmacokinetics of phenytoin in rabbits. Byrav, DS; Joshi, R; Medhi, B; Prakash, A, )	0.82
"To confirm whether 7 days of phenytoin, an enzyme inducer, would decrease the elimination half-life of single-dose nevirapine and to investigate its effect on the development of nevirapine resistance in pregnant, HIV-infected women."	( Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. Aitken, S; Burger, DM; Chunda, C; Fillekes, Q; Gibb, DM; Kankasa, C; Kisanga, ER; Muro, EP; Thomason, MJ; Walker, AS, 2013)	1
"In a pharmacokinetic pilot trial (NCT01187719), HIV-infected, antiretroviral (ARV)-naive pregnant women ≥18 years old from Zambia and Tanzania and with CD4 cell counts >350 cells/mm(3) were randomized 1 : 1 to a control (zidovudine pre-delivery, single-dose nevirapine/zidovudine/lamivudine at delivery and zidovudine/lamivudine for 7 days post-delivery) or an intervention (control plus 184 mg of phenytoin once daily for 7 days post-delivery) group."	( Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. Aitken, S; Burger, DM; Chunda, C; Fillekes, Q; Gibb, DM; Kankasa, C; Kisanga, ER; Muro, EP; Thomason, MJ; Walker, AS, 2013)	0.88
" The GM (95% CI) half-life of nevirapine was 63."	( Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. Aitken, S; Burger, DM; Chunda, C; Fillekes, Q; Gibb, DM; Kankasa, C; Kisanga, ER; Muro, EP; Thomason, MJ; Walker, AS, 2013)	0.71
"Adding 7 days of an enzyme inducer to single-dose nevirapine to prevent mother-to-child transmission of HIV significantly reduced subtherapeutic nevirapine levels by shortening the half-life of nevirapine."	( Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. Aitken, S; Burger, DM; Chunda, C; Fillekes, Q; Gibb, DM; Kankasa, C; Kisanga, ER; Muro, EP; Thomason, MJ; Walker, AS, 2013)	0.71
" Physiologically based pharmacokinetic (PBPK) modeling offers a means to dynamically integrate the complex interplay of the processes determining oral absorption."	( Incorporation of physiologically based pharmacokinetic modeling in the evaluation of solubility requirements for the salt selection process: a case study using phenytoin. Chiang, PC; Wong, H, 2013)	0.59
"To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA)."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.8
" Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
"Although both POPPK and physiologically based pharmacokinetic (PBPK) models can account for age and other covariates within a paediatric population, they generally do not account for real-time growth and maturation of the individuals through the time course of drug exposure; this may be significant in prolonged neonatal studies."	( Changes in individual drug-independent system parameters during virtual paediatric pharmacokinetic trials: introducing time-varying physiology into a paediatric PBPK model. Abduljalil, K; Jamei, M; Johnson, TN; Rostami-Hodjegan, A, 2014)	0.4
" Colesevelam (3750mg once daily) was dosed throughout the pharmacokinetic sampling period."	( Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. He, L; Lee, J; Mendell-Harary, J; Tao, B; Walker, J; Wickremasingha, P; Wight, D, 2014)	0.62
"For all six test drugs, 90% CIs for geometric least-squares mean ratios of AUC and Cmax for the measured analytes were within specified limits, indicating no interaction between the test drug and colesevelam."	( Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. He, L; Lee, J; Mendell-Harary, J; Tao, B; Walker, J; Wickremasingha, P; Wight, D, 2014)	0.62
" Although the phenytoin study indicated no pharmacokinetic interaction, phenytoin should continue to be taken ≥4h before colesevelam in accordance with current prescribing information."	( Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. He, L; Lee, J; Mendell-Harary, J; Tao, B; Walker, J; Wickremasingha, P; Wight, D, 2014)	0.98
" This study aimed to characterize the pharmacokinetics of posaconazole in adults and investigate factors that influence posaconazole pharmacokinetics byusing a population pharmacokinetic approach."	( Understanding variability in posaconazole exposure using an integrated population pharmacokinetic analysis. Brüggemann, RJ; Burger, DM; Dolton, MJ; McLachlan, AJ, 2014)	0.4
" A population pharmacokinetic approach was used to analyze paired protein-unbound and total phenytoin plasma concentrations (n = 146 each) from 32 critically ill children (0."	( Population pharmacokinetics of phenytoin in critically ill children. Charles, B; Foster, K; Hennig, S; Lister, B; Norris, R; Riney, K; Tu, Q; van Breda, K, 2015)	0.92
" We genotyped normal and epileptic patient cohorts of monoethnic population of Kashmir valley for CYP2C9 gene and allelic polymorphism and investigated the effect of CYP2C9*2 and *3 polymorphism on the Pharmacokinetic and therapeutic and/or adverse pharmacodynamic responses to Phenytoin in the idiopathic epilepsy patients."	( Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic approach to pharmacovigilance. Andrabi, KI; Jan, TR; Kousar, S; Wafai, ZA; Wani, MA, 2015)	0.81
" Phenytoin pharmacokinetic (PK) analysis in idiopathic epilepsy patients was done using a validated EMIT assay technique."	( Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic approach to pharmacovigilance. Andrabi, KI; Jan, TR; Kousar, S; Wafai, ZA; Wani, MA, 2015)	1.54
"The population pharmacokinetic model reported here was developed using data from 2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the impact of concomitant therapy with enzyme-inducing antiepileptic drugs (EIAEDs) on irinotecan pharmacokinetics."	( Quantification of the impact of enzyme-inducing antiepileptic drugs on irinotecan pharmacokinetics and SN-38 exposure. Ames, MM; Berg, AK; Buckner, JC; Galanis, E; Jaeckle, KA; Reid, JM, 2015)	0.42
" The purpose of the present study is to develop a physiologically based pharmacokinetic (PBPK) model for atorvastatin and its two primary metabolites, 2-hydroxy-atorvastatin acid and atorvastatin lactone, using in vitro and in vivo data."	( Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for atorvastatin and its metabolites. Zhang, T, 2015)	0.42
"To use a physiologically based pharmacokinetic (PBPK) modelling system to predict the serum levels achieved by two different intravenous loading doses of phenytoin."	( Comparing paediatric intravenous phenytoin doses using physiologically based pharmacokinetic (PBPK) modelling software. Appleton, R; Batchelor, H; Hawcutt, DB, 2015)	0.9
"A phenytoin pharmacokinetic model was used in the Simcyp population-based ADME simulator, simulating 100 children age 2-10 years receiving intravenous phenytoin (18 and 20mg/kg)."	( Comparing paediatric intravenous phenytoin doses using physiologically based pharmacokinetic (PBPK) modelling software. Appleton, R; Batchelor, H; Hawcutt, DB, 2015)	1.42
" The present study was performed to investigate the safety, tolerability, and pharmacokinetic profiles of rapid intravenous loading of fosphenytoin in SAH patients."	( Safety, Tolerability, and Pharmacokinetics of Fosphenytoin Loading in Patients With Subarachnoid Hemorrhage. Chun, YI; Ji, M; Kim, DW; Kim, TE, )	0.59
" The present study aims to establish a population pharmacokinetic (PPK) model of oral phenytoin in patients with intracranial tumor during the early periods, the first week, of post-craniotomy to optimize phenytoin dosage regimen."	( Population Pharmacokinetics of Phenytoin Based on NONMEM in Patients with Intracranial Tumor During the First Week of Post-Craniotomy. Huang, YA; Lei, Z; Li, L; Li, ZD; Liu, M; Wan, JH, 2016)	0.94
" We sought to develop a pharmacokinetic model of the interaction between phenytoin and capecitabine."	( Pharmacokinetic model analysis of interaction between phenytoin and capecitabine. Fukui, E; Hori, S; Ikenishi, M; Kawahara, K; Matsuyama, K; Miki, A; Miyazaki, S; Nakatsuka, E; Ohtori, T; Sakurai, M; Satoh, H; Sawada, Y; Ueda, M; Ueda, R, 2016)	0.91
" A systematic approach was developed to characterize the TI of a drug using therapeutic drug monitoring and electronic health record (EHR) data with pharmacokinetic (PK) modeling."	( Use of Therapeutic Drug Monitoring, Electronic Health Record Data, and Pharmacokinetic Modeling to Determine the Therapeutic Index of Phenytoin and Lamotrigine. Berezny, A; Cohen-Wolkowiez, M; Gonzalez, D; Greenberg, RG; Guptill, JT; Hill, KD; Hornik, CP; Jiang, W; Ku, LC; Melloni, C; Wu, H; Zheng, N, 2016)	0.64
" A population pharmacokinetic (PPK) analysis was performed to improve the topiramate dosage adjustment for individualized treatment."	( Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data. Ikeda, A; Ito, S; Matsubara, K; Sugimoto, M; Takeuchi, M; Yamamoto, S; Yano, I; Yonezawa, A, 2017)	0.46
" The impacts of CYP2C19 and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation."	( Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region. Dagenais, R; Elewa, H; Ensom, MHH; Wilby, KJ, 2017)	0.96
" Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human, and to predict drug concentration-time profiles in multiple CNS compartments on available human data of four drugs (acetaminophen, oxycodone, morphine and phenytoin)."	( Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach. Beukers, MW; Danhof, M; de Lange, ECM; Huntjens, DR; Kokki, H; Kokki, M; Krauwinkel, W; Proost, JH; Välitalo, PA; van Hasselt, JGC; Vermeulen, A; Wong, YC; Yamamoto, Y, 2018)	0.66
"We present a physiologically-based pharmacokinetic model (PBPK) of estradiol, and validate it against plasma kinetics in humans following intravenous and oral exposure."	( Linking physiologically-based pharmacokinetic and genome-scale metabolic networks to understand estradiol biology. Plant, NJ; Sier, JH; Thumser, AE, 2017)	0.46
"Retrospective, population pharmacokinetic analysis."	( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population. Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018)	1.1
"Population pharmacokinetic analysis was performed with NONMEM v7."	( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population. Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018)	1.1
" A pharmacokinetic model with two compartments, allometrically scaled fat-free mass on all parameters, and serum creatinine and concomitant phenobarbital use on clearance had the best fit."	( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population. Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018)	1.1
" This case highlights the possible pharmacokinetic interaction between phenytoin intake and Tc-sestamibi, resulting in faster hepatic clearance of the radiotracer."	( Phenytoin Could Potentially Increase Hepatic Clearance of 99mTc-Sestamibi in Myocardial Perfusion Imaging. Kavanal, AJ; Mittal, BR; Parmar, M; Singh, D; Sood, A, 2018)	2.16
" for population pharmacokinetic modeling."	( Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients. Alotaibi, M; Alqahtani, S; Alsultan, A; Alzaidi, T, 2019)	0.87
"The population pharmacokinetic model of phenytoin in Saudi patients found significant interindividual variability between subjects, which was affected by the patients' age, body weight, and VPA cotherapy as the most significant covariates on phenytoin Vmax and Km."	( Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients. Alotaibi, M; Alqahtani, S; Alsultan, A; Alzaidi, T, 2019)	1.14
" The aim of this study was to develop a population pharmacokinetic (PPK) model to describe serum phenytoin concentrations after the intravenous administration of fosphenytoin in adult and elderly epileptic patients."	( Population Pharmacokinetic Analysis of Phenytoin After Intravenous Administration of Fosphenytoin in Adult and Elderly Epileptic Patients. Higuchi, K; Hirakawa, M; Hirota, T; Ieiri, I; Kakara, M; Kashihara, Y; Yamashita, D, 2019)	1
"Background Valproic acid is one of several antiepileptic medications requiring therapeutic drug monitoring due to its complex and wide pharmacokinetic interindividual variability."	( Estimation of apparent clearance of valproic acid in adult Saudi patients. Alandas, N; Alqahtani, S; Alsultan, A, 2019)	0.51
"This study aimed to re-establish a Population Pharmacokinetic (PPK) model of oral phenytoin to further optimize the individualized medication regimen based on our previous research."	( The Evolution of Population Pharmacokinetic Model of Oral Phenytoin for Early Seizure Prophylaxis Post-Craniotomy. Ji, S; Jin, H; Li, Z; Song, G; Wang, C, 2019)	0.98
" Values for total clearance of compounds from plasma should be one of the most important pharmacokinetic parameters for predictions."	( Predicted values for human total clearance of a variety of typical compounds with differently humanized-liver mouse plasma data. Ito, S; Iwamoto, K; Kamimura, H; Mizunaga, M; Nakayama, K; Negoro, T; Nishiwaki, M; Nomura, Y; Suemizu, H; Yamazaki, H; Yoneda, N, 2020)	0.56
" The alterations in pharmacokinetic parameters (maximum serum concentration, area under the curve, clearance) of AEDs were also found with co-administration of HECA."	( Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. Agarwal, A; Arora, R; Ganeshan N, S; Gupta, YK; Kaleekal, T; Kumar, R; Sarangi, SC, 2021)	0.83
" But, alteration in pharmacokinetic parameters revel that needs critical medical supervision to avoid any toxic reactions."	( Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. Agarwal, A; Arora, R; Ganeshan N, S; Gupta, YK; Kaleekal, T; Kumar, R; Sarangi, SC, 2021)	0.83
" Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy."	( Population Pharmacokinetics of Levetiracetam: A Systematic Review. Jiao, Z; Li, ZR; Wang, CY; Zhu, X, 2021)	0.62
"The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates."	( Population Pharmacokinetics of Levetiracetam: A Systematic Review. Jiao, Z; Li, ZR; Wang, CY; Zhu, X, 2021)	0.62
" Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults."	( Population Pharmacokinetics of Levetiracetam: A Systematic Review. Jiao, Z; Li, ZR; Wang, CY; Zhu, X, 2021)	0.62
" The objective of this work was to evaluate predictive performance of two early concentrations and prior pharmacokinetic (PK) information for estimating early exposure."	( A pharmacokinetic simulation study to assess the performance of a sparse blood sampling approach to quantify early drug exposure. Brundage, RC; Chamberlain, JM; Cloyd, JC; Coles, LD; Elm, JJ; Ivaturi, V; Kapur, J; Sathe, AG; Silbergleit, R, 2021)	0.62
" Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity."	( A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children. Lattanzi, S; Zaccara, G, 2021)	0.62
" In this context, pharmacokinetic interactions between these drugs may occur."	( Pharmacokinetic Interactions Between Antiseizure and Psychiatric Medications. Franco, V; Zaccara, G, 2023)	0.91
" Indeed, because of its interesting pharmacokinetic properties, it is often used outside of the labeled indications, notably in the neurocritical setting as prophylaxis of epileptic seizures."	( Pharmacokinetic considerations surrounding the use of levetiracetam for seizure prophylaxis in neurocritical care - an overview. Amadori, E; D'Onofrio, G; Lattanzi, S; Riva, A; Rose, K; Striano, P; Verrotti, A, 2022)	0.72
"A literature search was conducted and the most relevant studies on the pharmacokinetic properties of LEV were selected by two independent investigators."	( Pharmacokinetic considerations surrounding the use of levetiracetam for seizure prophylaxis in neurocritical care - an overview. Amadori, E; D'Onofrio, G; Lattanzi, S; Riva, A; Rose, K; Striano, P; Verrotti, A, 2022)	0.72
"LEV has a 'near-ideal' pharmacokinetic profile, which makes it an attractive drug for ASM prophylaxis in neurocritical care."	( Pharmacokinetic considerations surrounding the use of levetiracetam for seizure prophylaxis in neurocritical care - an overview. Amadori, E; D'Onofrio, G; Lattanzi, S; Riva, A; Rose, K; Striano, P; Verrotti, A, 2022)	0.72

Compound-Compound Interactions

Phenobarbital in combination with phenytoin (2.5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/ kg) was tested. There were no statistically significant differences in carbamazepine, carbazepine epoxide, and pheny toin pharmacokinetic parameters when either drug was administered alone or in combination.

Excerpt	Reference	Relevance
" The binding of digitoxin and cardioactive metabolites to serum proteins was studied using equilibrium dialysis (an in vitro chemical assay) alone and in combination with a modified 86Rb method."	( Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin. Storstein, L, 1976)	0.26
" Omeprazole contains a benzimidazole moiety and thus has the potential to interact with the cytochrome P-450 enzyme group."	( Clinical implications of drug interactions with the cytochrome P-450 enzyme system associated with omeprazole. Humphries, TJ, 1991)	0.28
" The clinician should be aware of important drug-drug interactions prior to prescribing NSAIDs."	( Drug interactions with non steroidal anti-inflammatory drugs (NSAIDs). Weinblatt, ME, 1989)	0.28
"Rifampin, a potent inducer of the hepatic microsomal system, has been shown to cause clinically important interactions when combined with other drugs, including oral anticoagulants, oral contraceptives, digitoxin, methadone hydrochloride, sulfonylureas, and barbiturates."	( Update on rifampin drug interactions. Baciewicz, AM; Bekemeyer, WB; Self, TH, 1987)	0.27
"5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/kg), and those of phenobarbital (10 and 20 mg/kg) in combination with phenytoin (2."	( Effects of phenobarbital in combination with phenytoin or valproic acid on the delayed-matching-to-sample performance of pigeons. Karas, CA; Picker, M; Poling, A, 1986)	0.74
"A new electrochemical immunoassay combined with column liquid chromatography has been developed for the determination of phenytoin in human serum."	( Electrochemical immunoassay combined with column liquid chromatography: determination of phenytoin in human serum. Hatsumura, H; Hosokawa, M; Michida, T; Sayo, H, 1987)	0.7
" However, because PB had a markedly lower TI than PHT in this model, the TI of the drug combination was lower than the TI of PHT."	( Antiepileptic drug combinations and experimental background: the case of phenobarbital and phenytoin. Bourgeois, BF, 1986)	0.49
" Diphenyl hydantoin is often combined with barbiturates to treat epilepsy."	( [Drug interactions in the use of steroid hormones, especially oral contraceptives]. Bolt, HM, 1985)	0.27
" Phenytoin in combination with other drugs (anticonvulsives, antibiotics etc."	( [Effects of drug interaction in infancy (author's transl)]. Alterthum, K; Bauer, P; Stünkel, S; Windorfer, A, 1980)	1.17
" These effects, combined with the common use of cimetidine in clinical practice, make the risk of adverse drug interactions a relatively frequent risk in the clinical setting."	( Drug interactions involving cimetidine--mechanisms, documentation, implications. Greene, W, 1984)	0.27
" These parameters were compared with literature and in vivo experimental values, and the results suggest that the model should be suitable for the study of metabolic drug-drug interactions occurring in the rat liver."	( An assessment of the suitability of a modified technique of in situ rat-liver perfusion for the study of certain hepatic drug-drug interactions. Fairweather, I; Maguire, TA; Swanton, JG; Temple, DJ, 1984)	0.27
" These results show that oxazepam glucuronyl transferase activity is increased by treatment with phenytoin alone or in combination with phenobarbitone in epileptic patients."	( Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Hawksworth, GM; Khir, AS; Petrie, JC; Scott, AK; Steele, WH, 1983)	0.71
"Valproic acid undergoes drug-drug interactions with most of the commonly used anticonvulsants."	( Drug interactions with valproic acid. Koch, KM; Levy, RH, 1982)	0.26
" 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
"The purpose of this case report is to present an example of a child with receptive and expressive language problems occurring in combination with a seizure disorder."	( Receptive and expressive language problems occurring in combination with a seizure disorder: a case report. Jordan, LS, 1980)	0.26
" Different mechanisms have to be considered as causes for potential drug-drug interactions."	( Lack of pantoprazole drug interactions in man. Bliesath, H; Hartmann, M; Huber, R; Radtke, HW; Steinijans, VW; Wurst, W; Zech, K, 1994)	0.29
" Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions."	( Clinically significant pharmacokinetic drug interactions with carbamazepine. An update. Perucca, E; Pisani, F; Spina, E, 1996)	0.29
" There were no statistically significant differences in carbamazepine, carbamazepine epoxide, and phenytoin pharmacokinetic parameters when either drug was administered alone or in combination with tiagabine."	( Lack of pharmacokinetic drug interactions between tiagabine and carbamazepine or phenytoin. Boellner, SW; Cao, GX; Cato, A; Guenther, HJ; Gustavson, LE; Qian, JX; Sommerville, KW, 1998)	0.74
"The effect of nitrendipine (NTP) alone and in combination with phenytoin (PHT) and valproate (VPA) against maximal electroshock seizures (MES) was studied in rats."	( Anticonvulsant and psychomotor activity of nitrendipine alone and in combination with phenytoin and valproate in rats. Balakrishnan, S; Bhargava, VK; Pandhi, P, )	0.59
"The effect of nimodipine alone and in combination with diazepam or phenytoin was tested in the electroshock-induced mouse model of status epilepticus."	( Anticonvulsant effect of nimodipine alone and in combination with diazepam and phenytoin in a mouse model of status epilepticus. Khosla, P; Pandhi, P, 2000)	0.77
"Many fluoroquinolone antibiotics are inhibitors of cytochrome P450 enzyme systems and may produce potentially important drug interactions when administered with other drugs."	( Drug interactions with clinafloxacin. Abel, R; Alvey, CW; Bron, NJ; Hounslow, NJ; Koup, JR; Randinitis, EJ; Rausch, G; Sedman, AJ; Vassos, AB, 2001)	0.31
"A prospective, randomized, 3-period crossover study was conducted in 16 healthy volunteers with phenytoin alone, phenytoin in combination with losartan, and losartan alone."	( Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers. Fischer, JD; Fischer, TL; Goldstein, JA; Graff, DW; Greenwood, R; Parnell, KJ; Patterson, JH; Pieper, JA; Rodgers, JE, 2002)	0.81
" Subsequent replacement of hypertonic saline with normal saline and salt tabs in combination with phenytoin allowed gradual correction of serum sodium without any subsequent seizures or neurological complications."	( Therapy with hypertonic saline in combination with anti-convulsants for hyponatremia-induced seizure: a case report and review of the literature. Tokeshi, J; Youn, KS, 2002)	0.53
" This study investigates the effect of pretreatment with celecoxib alone, or in combination with phenytoin, on electroshock-induced convulsions."	( Anticonvulsant action of celecoxib (alone and in combination with sub-threshold dose of phenytoin) in electroshock induced convulsion. Malhotra, S; Pandhi, P; Shafiq, N, 2003)	0.76
"Phenytoin is an anticonvulsant drug known to interact with many other drugs."	( Studying long-term effect of phenytoin either alone or combined with ascorbic acid on the anesthetic effect of urethane in rats. Abdulla, MM; El Desoky, ES, 2004)	2.06
"This study was aimed at evaluating the body temperature of mice following the injection of LY 300164, an AMPA/kainate receptor antagonist, alone or in combination with carbamazepine or diphenylhydantoin."	( Influence of LY 300164 alone or in combination with carbamazepine or diphenylhydantoin on the body temperature in mice. Czuczwar, SJ; Luszczki, JJ; Swiader, MJ; Wierzchowska-Cioch, E; Zwolan, A, 2004)	0.32
" Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ)."	( Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Alvey, CW; Bockbrader, HN; Brodie, MJ; Bron, NJ; Gibson, GL; Hounslow, NJ; Posvar, EL; Randinitis, EJ; Wesche, DL; Wilson, EA, 2005)	0.75
" PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug-drug interactions."	( Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Alvey, CW; Bockbrader, HN; Brodie, MJ; Bron, NJ; Gibson, GL; Hounslow, NJ; Posvar, EL; Randinitis, EJ; Wesche, DL; Wilson, EA, 2005)	0.55
" Drug-drug interactions (DDIs) caused by induction of CYP3A4 can result in decreased exposure to coadministered drugs, with potential loss of efficacy."	( Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. de Morais, SM; Fahmi, OA; Liras, JL; Maurer, TS; Mills, JB; Ripp, SL; Trevena, KA, 2006)	0.33
" This study evaluated lamotrigine alone or in combination with phenobarbital, phenytoin, or the glutamate antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) for a proapoptotic action in the developing rat brain."	( Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain. Gale, K; Katz, I; Kim, J; Kondratyev, A, 2007)	0.8
"Most proton pump inhibitors are extensively metabolized by cytochrome P450 (CYP) isoenzymes, as are many other drugs, giving rise to potential drug-drug interactions."	( Drug interaction studies with dexlansoprazole modified release (TAK-390MR), a proton pump inhibitor with a dual delayed-release formulation: results of four randomized, double-blind, crossover, placebo-controlled, single-centre studies. Gunawardhana, L; Lee, RD; Mulford, D; Vakily, M; Wu, J, 2009)	0.35
"Mean C(max) and AUC values were generally similar for each test substrate when administered with multiple once-daily doses of dexlansoprazole MR or placebo."	( Drug interaction studies with dexlansoprazole modified release (TAK-390MR), a proton pump inhibitor with a dual delayed-release formulation: results of four randomized, double-blind, crossover, placebo-controlled, single-centre studies. Gunawardhana, L; Lee, RD; Mulford, D; Vakily, M; Wu, J, 2009)	0.35
" To assess drug-drug interactions, co-administration experiments were conducted with ketoconazole and either propranolol or erythromycin."	( Exploration of the African green monkey as a preclinical pharmacokinetic model: oral pharmacokinetic parameters and drug-drug interactions. Bhadresa, S; Coon, DJ; Lawrence, MS; Magiera, D; Struharik, M; Ward, KW, 2009)	0.35
"To evaluate the effects of high-frequency electrical stimulation (HFS) in both ventral hippocampi, alone and combined with a subeffective dose of antiepileptic drugs, during the status epilepticus (SE) induced by lithium-pilocarpine (LP)."	( Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats. Alcantara-Gonzalez, D; Cuellar-Herrera, M; Neri-Bazan, L; Peña, F; Rocha, L, 2010)	0.36
" One minute following pilocarpine injection, HFS (pulses of 60 mus width at 130 Hz at subthreshold intensities and applied during 3 h) was applied alone or combined with subeffective doses of antiepileptic drugs."	( Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats. Alcantara-Gonzalez, D; Cuellar-Herrera, M; Neri-Bazan, L; Peña, F; Rocha, L, 2010)	0.36
" This effect was not evident when HFS was combined with phenytoin (33."	( Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats. Alcantara-Gonzalez, D; Cuellar-Herrera, M; Neri-Bazan, L; Peña, F; Rocha, L, 2010)	0.61
" The drug combination elevated the plasma level of PHT in a patient on chemotherapy with capecitabine for colorectal cancer."	( [A case of toxicity caused by drug interaction between capecitabine and phenytoin in patient with colorectal cancer]. Fukui, E; Kawahara, K; Sakurai, M; Ueda, R; Yamada, R, 2011)	0.6
" The cases were categorized into OXC monotherapy (n = 78), OXC in combination with EIAED (n = 73), and OXC in combination with non-EIAED (n = 103)."	( Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy. Hong, SB; Huh, W; Joo, EY; Kim, JR; Kim, SR; Ko, JW; Lee, SY; Park, KJ; Seo, DW, )	0.13
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012)	0.38
" For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
"When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
"The prediction of drug-drug interactions mediated by the induction or inhibition of cytochrome P450 enzymes is of great relevance in the development of new drugs."	( HepaRG cell line as an in vitro model for screening drug-drug interactions mediated by metabolic induction: amiodarone used as a model substance. Alves, G; Falcão, A; Ferreira, A; Rodrigues, M; Silvestre, S, 2014)	0.4
" The model was used to predict the pharmacokinetic profiles and drug-drug interaction (DDI) effect for atorvastatin and its metabolites in different DDI scenarios."	( Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for atorvastatin and its metabolites. Zhang, T, 2015)	0.42
" Concomitant use of erlotinib and the antiepileptic drug phenytoin, an inducer of CYP3A4, may result in a drug-drug interaction accompanied by changes in the blood concentrations of both drugs."	( Drug interaction between erlotinib and phenytoin for brain metastases in a patient with nonsmall cell lung cancer. Homma, M; Kaburagi, T; Kurosawa, A; Ohgami, M, 2016)	0.95
" In another independent set of experiments, similar results of drug combination responses were also found."	( Anti-Epileptic Drug Combination Efficacy in an In Vitro Seizure Model - Phenytoin and Valproate, Lamotrigine and Valproate. French, CR; O'Brien, TJ; Taing, KD; Williams, DA, 2017)	0.69
"Multi-drug combinations often make chemotherapy difficult owing to drug-drug interactions (DDIs)."	( Drug-drug interactions among drugs prescribed for nontuberculous mycobacterial infection and epilepsy: A case report. Hatanaka, M; Ikeda, R; Matsumoto, N; Oda, Y; Sonoda, J; Tazaki, T; Yoshikawa, N, 2019)	0.51
" Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity."	( A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children. Lattanzi, S; Zaccara, G, 2021)	0.62
"The drug-drug interaction (DDI) risk of phenytoin with several topical formulations of miconazole is still unclear."	( Risk prediction of drug-drug interaction potential of phenytoin and miconazole topical formulations. Bi, C; Cao, X; Cui, S; Jiang, L; Li, W; Liu, Y; Wang, X; Wang, Z, 2021)	1.14
" In this study, we established a quantitative analysis method for phenytoin sodium (PS) based on partial least-squares (PLS) and linear regression (LR) models combined with SERS."	( Rapid detection of phenytoin sodium by partial-least squares and linear regression models combined with surface-enhanced Raman spectroscopy. Chen, Y; Deng, B; Li, D; Wang, X; Wen, Y; Zhang, Q, 2023)	1.48
"This case highlights the strong and important drug-drug interaction between tacrolimus and nirmatrelvir/ritonavir leading to toxic levels of tacrolimus."	( Tacrolimus Drug-Drug Interaction with Nirmatrelvir/Ritonavir (Paxlovid™) Managed with Phenytoin. Carroll, E; McCabe, D; Sindelar, M, 2023)	1.13

Bioavailability

Peytoin has an important effect on the pharmacokinetics of ivabradine in healthy subjects, reducing its bioavailability by approximately 70%. The effect of a change in bioavailability of phenytoin sodium formulations on steady state serum concentrations was assessed.

Excerpt	Reference	Relevance
" There was no consistent effect on the metabolism of dicumarol following treatment with amitriptyline or nortriptyline although the bioavailability of dicumarol appeared to be increased."	( Effects of tricyclic antidepressants on drug metabolism. Birkett, DJ; Graham, GG; Pond, SM; Wade, DN, 1975)	0.25
"The bioavailability of three commercial products of phenytoin (Epanutin, sodium salt; Phenhydan, calcium salt; Zentropil, free acid) was studied relative to a standard solution of sodium phenytoin."	( The bioavailability of phenytoin. Eichelbaum, M; Fröscher, W; Gugler, R; Hildenbrand, G, 1977)	0.82
" New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses."	( Recent advances in drug therapy for epilepsy. Bruni, J, 1979)	0.52
" It has certain physicochemical characteristics which make it liable to bioavailability problems."	( Bioavailability of phenytoin: clinical pharmacokinetic and therapeutic implications. Neuvonen, PJ, )	0.46
" Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in Scandinavia."	( Clinical pharmacokinetics of phenytoin. Richens, A, )	0.42
" A bioavailability study in seven healthy volunteers showed immediate absorption of the treated drug but a 1-hr absorption lag time for the pure drug."	( In vitro and in vivo availability of hydrophilized phenytoin from capsules. Broersma, P; Lagas, M; Lerk, CF; Lie-a-Huen, L; Zuurman, K, 1979)	0.51
"The effects of bihourly administration of gluconate calcium and tow magnesium-aluminum-containing acids on the bioavailability of a single capsule dose of phenytoin sodium were determined in two normal volunteers."	( Effect of calcium and antacids on phenytoin bioavailability. Chapron, DJ; Hohnadel, DC; Kramer, PA; Mariano, SL, 1979)	0.74
"Significant differences in bioavailability were observed in dogs when phenytoin crystals of different particle size were administered."	( Bioavailability of phenytoin in dogs: effect of crystal form and particle size. Belpaire, F; Chakrabarti, S; Moerman, E, 1979)	0.82
"Model-dependent relationships describing the effects of absorption rate and dosing interval on steady-state phenytoin plasma concentrations are presented and discussed."	( Steady-state plasma concentrations as a function of the absorption rate and dosing interval for drugs exhibiting concentration-dependent clearance: consequences for phenytoin therapy. Rector, TS; Sawchuk, RJ, 1979)	0.67
" The bioavailability of a brand of phenytoin tablets used in Finland was improved in 1976."	( Effect of increased bioavailability of phenytoin tablets on serum phenytoin concentration in epileptic out-patients. Bardy, A; Lehtovaara, R; Neuvonen, PJ, 1979)	0.81
"The bioavailability of seven phenytoin (DPH) formulations, five brands of tablets and two suspensions, was measured in a cross-over study with six healthy volunteers."	( Factors affecting the bioavailability of phenytoin. Elfving, SM; Neuvonen, PJ; Pentikäinen, PJ, 1977)	0.81
" Whereas the absorption was almost identical for both preparations in the fasting state, it differed significantly after ingestion of a breakfast: the one preparation, DPH-A, was less well absorbed than the other, DPH-B (7,9 mcg/ml serumconcentration 5 hours after oral administration of 5 mg/kg DPH-B versus 5,7 mcg/ml serumconcentration 5 hours after administration of 5 mg/kg DPH-A)."	( Influences on the absorption of diphenylhydantoin preparations. Stünkel, S; Weimann, HM; Windorfer, A, 1978)	0.26
" The difference in bioavailability reduced the drug requirement to 55% of the previous dose."	( An unusual case of phenytoin intoxication. Albani, M, 1978)	0.59
"The dissolution rates of various commercially available oral phenytoin preparations were determined in vitro and compared with the in vivo data for the bioavailability obtained from volunteers in a subchronic study."	( [Dissolution rates and bioavailability of phenytoin preparations (author's transl)]. Brandau, R; Wehnert, HU, 1979)	0.77
" It was found that the relative degree of bioavailability of Phenytoin in relation to Epanutin as a standard is 70,7 +/- 6,3% (SD)."	( [Evaluation of the bioavailability of Polfa phenytoin tablets]. Lazowski, J; Lypka, A; Pakszys, W; Zadrozyńska, E, )	0.63
" The absorption rate and fraction are very much dependent on the pharmaceutical preparation, and changes of brand may alter the plasma level of phenytoin in spite of unaltered dose."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.46
" The ground mixtures significantly improved the bioavailability of phenytoin."	( Dissolution behavior and bioavailability of phenytoin from a ground mixture with microcrystalline cellulose. Arita, T; Nakai, Y; Nakano, M; Takayama, Y; Yamamoto, K, 1976)	0.75
"In order to evaluate the bioavailability of four different brands of phenytoin (diphenylhydantoin, DPH) tablets single doses of 600 mg DPH in acid form were given to six volunteers in a cross-over study."	( Bioavailability of four brands of phenytoin tablets. Elfving, SM; Neuvonen, PJ; Pentikäinen, PJ, 1975)	0.77
" The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57."	( Phenytoin: pharmacokinetics and bioavailability. Azarnoff, DL; Gugler, R; Manion, CV, 1976)	1.7
" However, absolute bioavailability of the drug was not different in both age groups (72."	( [Phenytoin pharmacokinetics in young and older adults]. Estruch, J; Galdames, D; Martinetti, A; Saavedra, I, 1992)	1.19
" Through pharmacokinetic analyses, the decreased AUC and increased Vz/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered."	( Effect of single- and multiple-dose carbamazepine on the pharmacokinetics of diphenylhydantoin. Huang, JD; Lai, ML; Lin, TS, 1992)	0.49
"Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine."	( Bioavailability and bioinequivalence of drug formulations in small animals. Watson, AD, 1992)	0.28
" Consequences of this observation for relative bioavailability studies of drugs with nonlinear pharmacokinetic properties are discussed."	( Bioavailability studies of drugs with nonlinear pharmacokinetics: I. Tracer dose AUC varies directly with serum concentration. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Schumacher, GE; Szabo, GK, 1992)	0.28
"A comparative study of the bioavailability of seven formulations of phenytoin was carried out on 17 patients with epilepsy who were taking phenytoin regularly as part of their drug therapy."	( Bioavailability and dissolution of proprietary and generic formulations of phenytoin. Richens, A; Soryal, I, 1992)	0.75
" Since praziquantel, the drug used to treat neurocysticercosis, undergoes extensive liver first-pass metabolism, we carried out a prospective study to verify whether there was a decrease in oral bioavailability induced by carbamazepine and phenytoin."	( Phenytoin and carbamazepine decreased oral bioavailability of praziquantel. Bittencourt, PR; Diekmann, HW; Fernandes, AG; Gracia, CM; Jung, W; Martins, R, 1992)	1.91
" It could be due to a lower bioavailability (F) of the tested phenytoin preparations and/or a higher volume of distribution (Vd) in Chinese."	( Comparison on bioequivalence of four phenytoin preparations in patients with multiple-dose treatment. Huang, JD; Lai, ML; Tsai, JJ; Yang, YH, 1992)	0.8
"The problematic bioavailability of phenytoin's (5,5-diphenylhydantoin) oral formulations serves as a stimulus for examining new formulations and/or administration conditions that may provide more predictable absorption."	( Bioavailability study of a freeze-dried sodium phenytoin-milk formulation. Ismailos, G; Macheras, P; Reppas, C, 1991)	0.82
" While absorption rate was not important, each patient's dose ranges were extremely narrow, emphasizing that dose size was the dominant factor in the control of phenytoin levels."	( Computer-aided dosage form design. III. Feasibility assessment for an oral prolonged-release phenytoin product. Irvin, JR; Notari, RE, 1991)	0.7
"The NONMEM method, one of the methods used for analysis of population pharmacokinetics, was applied to the evaluation of the relative bioavailability of drug products."	( Application of the NONMEM method to evaluation of the bioavailability of drug products. Aoyagi, N; Ishii, M; Kaniwa, N; Ogata, H, 1990)	0.28
" The influence of weight, co-anticonvulsants on the maximum elimination rate (Vm) and age, co-anticonvulsants on the Michaelis-Menten constant (Km) and the influence of dosage form on the bioavailability (F) of PHT were investigated."	( Population pharmacokinetics of phenytoin from routine clinical data in Japan: an update. Aoyama, T; Higuchi, S; Yukawa, E, 1990)	0.57
" Assuming there were no changes in the bioavailability of amiodarone during continuous administration, these findings strongly suggest induction of amiodarone metabolism by phenytoin."	( Effect of phenytoin on the clinical pharmacokinetics of amiodarone. Gear, K; Hoyer, GL; Karol, MD; Marcus, FI; Nolan, PE, 1990)	0.88
"An alternative approach to bioavailability and bioequivalence assessment is presented."	( Alternative approach to relative bioavailability and bioequivalence evaluation, with drugs following Michaelis-Menten elimination kinetics. Fagiolino, P; Stareczek, S, 1990)	0.28
" The objectives of this investigation were to determine the absolute bioavailability and free fraction of PHT after intravenous (i."	( Absolute bioavailability of phenytoin after 3-phosphoryloxymethyl phenytoin disodium (ACC-9653) administration to humans. Brouwer, KL; Donn, KH; Dukes, GE; Jamerson, BD; Messenheimer, JA; Powell, JR, )	0.43
"The comparative bioavailability of two phenytoin products, Phenytoin Sodium (CAPS (Pvt) Ltd) and Epanutin (Parke-Davis (Pty) Ltd) was studied."	( A comparative bioavailability of 2 oral solid phenytoin dosage forms. Morton, DJ; Naik, D, 1989)	0.8
"41 h-1 and an absolute bioavailability (F) of 100."	( Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration. Achari, R; Bombassaro, AM; Boucher, BA; Rasmussen, SN; Turlapaty, P; Watridge, CB, 1989)	1.72
"The bioavailability of phenytoin from ACC-9653 versus intravenously administered sodium phenytoin was determined using a crossover design for intravenous and intramuscular administration of ACC-9653 to healthy volunteers."	( Bioavailability of ACC-9653 (phenytoin prodrug). Browne, TR; Davoudi, H; Donn, KH; Dougherty, CL; Dukes, GE; Evans, B; Evans, JE; Jamerson, B; Kres, J; McEntegart, CM, 1989)	0.88
" The bioavailability of the formulations varied from 43 to 54 per cent."	( Pharmacokinetics of three formulations of diphenylhydantoin in the dog. Mol, JA; Overduin, LM; van Gogh, H; van Nes, JJ, 1989)	0.28
" Steady-state intestinal membrane permeabilities were obtained in an in situ perfusion system and initial rates of intestinal tissue uptake were obtained in an in vitro everted ring system as rate of absorption parameters."	( Nutrient influences on rat intestinal phenytoin uptake. Aspacher, G; Fleisher, D; Griffin, H; McFadden, M; Sheth, N, 1989)	0.55
" The aim was to determine if there were systematic changes in the limits of the single dose confidence interval at steady state that would limit the usefulness of confidence intervals following a single dose in accurately predicting bioavailability following multiple dosing."	( Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics. Jackson, AJ, )	0.13
" The absolute bioavailability of phenytoin varied between 68 and 74%."	( A comparative study of the bioavailability of five different phenytoin preparations. Hirji, MR; Kuhn, S; Measuria, H; Mucklow, JC, 1985)	0.79
" The influence of weight on the maximum elimination rate (Vm) and age on the Michaelis-Menten constant (Km) or the influence of dosage form on the bioavailability (F) of phenytoin were investigated."	( Population pharmacokinetics of phenytoin from routine clinical data in Japan. Aoyama, T; Higuchi, S; Yukawa, E, 1989)	0.76
" We studied the effects of two administration schedules of an ENF on the bioavailability of PHT."	( Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability. Comstock, TJ; Fitzsimmons, WE; Garnett, WR; Karnes, HT; Krueger, KA; Pellock, JM, )	0.36
" The percent relative bioavailability of phenytoin with enteral feedings was 101."	( Influence of enteral feedings on phenytoin sodium absorption from capsules. Armstrong, EP; Iacono, RP; Nishimura, LY; Plezia, PM, 1988)	0.82
" It is concluded that cholestyramine does not significantly affect the bioavailability of a single dose of phenytoin."	( Lack of effect of cholestyramine on phenytoin bioavailability. Amione, C; Barzaghi, N; Frigo, GM; Lecchini, S; Monteleone, M; Perucca, E, 1988)	0.76
"The need for careful monitoring of plasma concentrations of phenytoin during use of the drug in the treatment of epilepsy is well recognized; there can be great intersubject variation in the absorption rate and clearance rate of the drug, and its therapeutic ratio is narrow."	( Comparative determination of phenytoin in plasma by fluorescence polarization immunoassay and high performance liquid chromatography. al-Turk, WA; Awidi, AS; Daradkeh, TK; Othman, S; Shaheen, O, 1987)	0.81
" The relative oral/intramuscular bioavailability of amitriptyline was only 13%, and the steady-state concentrations of this drug on four consecutive days were acutely subtherapeutic (i."	( Decreased drug absorption in a patient with Behçet's syndrome. Atiyeh, M; Chaleby, K; el-Yazigi, A, 1987)	0.27
" Bioavailability of prednisolone after the oral administration of prednisone and methylprednisolone ranged from 86% to 104% during anticonvulsant therapy."	( Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy. Bartoszek, M; Brenner, AM; Szefler, SJ, 1987)	0.27
" Patients were categorized into four groups for evaluation of the effect of potential bioavailability problems and length of dosing history (time over which serum concentration-time data were collected) on the ability to predict subsequent phenytoin concentrations."	( Evaluation of a Bayesian regression-analysis computer program using non-steady-state phenytoin concentrations. Clementi, WA; Godley, PJ; Godley, SE; Ludden, TM; Ramsey, RR, 1987)	0.68
" The likely causes of this fact were: too low doses prescribed (55% of the patients were given doses below the generally recommended), lower bioavailability of PHT (27% of patients had no therapeutic level of the drug in the serum, despite doses exceeding 5 mg/kg); or drug interaction."	( [Characteristics of the clinical features and pharmacological treatment of epileptics with frequent seizures]. Buksowicz, C; Horyd, W; Koziak, M; Kuran, W; Lipczyńska-Lojkowska, W; Niedzielska, K; Witkowska-Olearska, K, )	0.13
" The bioavailability and single dose pharmacokinetics of extended phenytoin sodium capsules (Dilantin Kapseals) and phenytoin oral suspension (Dilantin oral suspension) were compared in seven healthy adult volunteers."	( Single dose comparison of the relative bioavailability of phenytoin suspension and extended capsules. Comstock, TJ; Fitzsimmons, WE; Garnett, WR; Pellock, JM, )	0.61
" Certain physiochemical properties of phenytoin may lead to bioavailability changes."	( Review of alterations in oral phenytoin bioavailability associated with formulation, antacids, and food. Cacek, AT, 1986)	0.83
" Phenytoin bioavailability was studied following a single dose of phenytoin 500 mg po in nine normal subjects during a control period and when given with sucralfate."	( Effect of sucralfate on phenytoin bioavailability. Cuddy, PG; Glass, CJ; Hall, TG; Melethil, S, )	1.35
"The bioavailability of dexamethasone (DEX) has recently been demonstrated to be a critical factor in determining Dexamethasone Suppression Test (DST) status in psychiatric patients."	( Dexamethasone bioavailability: implications for DST research. Lowy, MT; Meltzer, HY, 1987)	0.27
"Adverse gastrointestinal symptoms from milk may reduce the bioavailability of phenytoin."	( Effect of simultaneously ingested milk on phenytoin bioavailability. Dasheiff, R; Dickinson, L; Dotson, R; Kang, H, 1985)	0.76
" Bioavailability is enhanced by food or propantheline."	( Nitrofurantoin. D'Arcy, PF, )	0.13
" The mechanisms responsible for these effects have not been elucidated and possibly include decreased bioavailability or compliance, increased metabolic clearance, or decreased plasma protein binding."	( Effects of pregnancy on antiepileptic drug utilization. Levy, RH; Yerby, MS, 1985)	0.27
"Crossover studies, following single oral doses given to 19 healthy volunteers were conducted to compare the bioavailability of three phenytoin preparations: DANTOIN and IDANTOIN (Teva, Israel) and EPANUTIN (Parke-Davis, USA)."	( Bioavailability of phenytoin: comparison between three preparations. Ackerman, Z; Frumerman, I; Garty, M; Kitzes, R; Levy, M; Shved, A, 1985)	0.8
"The effect of a change in bioavailability of phenytoin sodium formulations on steady state serum concentrations was assessed in two groups of neurosurgical patients (n = 20 and 12)."	( Phenytoin bioavailability assessed by steady state serum concentrations. Dany, S; Dinai, Y; Gapany, M; Halkin, H, 1985)	1.97
" The present stable-isotope methodology offered advantages for the estimation of absolute bioavailability of the oral phenytoin dose in patients, while normal therapy was continued and not withdrawn."	( Stable-isotope methodology for the bioavailability study of phenytoin during multiple-dosing regimens. Baba, S; Kasuya, Y; Mamada, K; Matsukura, M, 1985)	0.72
"Urinary excretion of p-hydroxyphenytoin and its glucuronide conjugate was measured in eight healthy young adults in a comparative bioavailability study of oral sodium phenytoin (approximately 5 mg/kg/dose)."	( Extent of urinary excretion of p-hydroxyphenytoin in healthy subjects given phenytoin. Dickinson, RG; Eadie, MJ; Hooper, WD; Maguire, B; Patterson, M, 1985)	0.83
" It is concluded that if, in a given patient, the p-HPPH level corresponds to the value expected from the PHT dose, it can be assumed that compliance and bioavailability are adequate and that the dose does not exceed Vmax."	( Michaelis-Menten kinetics and the steady-state serum phenytoin/hydroxyphenytoin ratio. Bourgeois, BF; Wad, N, 1985)	0.52
" The bioavailability of phenytoin preparations is not only depended on the type of the substance used (salt, free acid), but also on the excipients used for the preparation of tablets."	( [Bio-availability of phenytoin free-acid serum level determinations whilst using a lactose-based tablet-preparation (author's transl)]. Fritsch, G; Füger, G; Haidvogl, M; Urban, C, 1980)	0.89
" These mechanisms include: (1) impaired hepatic drug metabolism due to inhibition of hepatic microsomal enzymes, (2) reduced hepatic blood flow, resulting in decreased clearance of drugs that are highly extracted by the liver, (3) increased potential for myelosuppression when administered concurrently with other drugs capable of causing myelosuppression, and (4) altered bioavailability of acid-labile drugs."	( Review of cimetidine drug interactions. Darvey, DL; Sorkin, EM, 1983)	0.27
" Carbamazepine is well absorbed and largely metabolized."	( Pharmacokinetics of antiepileptic drugs. Neuvonen, PJ; Tokola, RA, 1983)	0.27
" The effect of protein on phenytoin dissolution may well affect the bioavailability of the drug."	( The effect of protein on the dissolution of phenytoin. Macheras, P; Rosen, A, 1984)	0.83
" Relative bioavailability for the conventional tablet in comparison with the microcrystallin was in the range of 48-80% during single dose administration and in the range 54-95% at steady-rate."	( A comparison between microcrystalline and conventional phenytoin preparations: relative bioavailability and steady-state plasma concentrations. Boréus, LO; Ehrnebo, M; Nergårdh, A; Theorell, K, 1980)	0.51
" However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability."	( Bioavailability and pharmacokinetics of phenytoin during pregnancy. Chalk, JB; de Wytt, C; Eadie, MJ; Lander, CM; Livingstone, I; Smith, MT; Symoniw, P, 1984)	0.54
" Apparent volume of distribution was similar in the two groups, but the group treated with phenytoin had an almost statistically significantly shorter dexamethasone mean terminal half-life, an approximately trebled mean plasma clearance, and a mean oral bioavailability of the steroid of only 33%, compared with a mean 84% oral bioavailability in those not receiving phenytoin."	( Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients. Brophy, T; Chalk, JB; Eadie, MJ; Ridgeway, K; Yelland, JD, 1984)	1.93
"Phenytoin bioavailability was evaluated in beagle dogs after oral and intravenous administrations of sodium phenytoin and two amino acyl esters and a disodium phosphate ester of 3-(hydroxymethyl)phenytoin (three prodrugs of phenytoin)."	( Phenytoin prodrugs V: In vivo evaluation of some water-soluble phenytoin prodrugs in dogs. Stella, VJ; Varia, SA, 1984)	3.15
" Studying the bioavailability of phenytoin in different age groups (infants, children, and adolescents) before and after ingestion of age-appropriate food showed an age-dependent absorption rate and extent, and an influence of the food upon the absorption pattern could be demonstrated."	( Oral phenytoin in infancy: dose requirement, absorption, and elimination. Albani, M; Wernicke, I, 1983)	1.06
"The drug diphenylhydantoin (phenytoin) (DPH) is thought to interfere with the bioavailability of dietary folate through an effect on intestinal folate deconjugation and/or monoglutamate folate transport."	( The effect of diphenylhydantoin (phenytoin) on the sequential stages of intestinal folate absorption. Cerda, JJ; Crick, WF; Nelson, EW; Streiff, RR; Wilder, BJ, 1983)	0.84
" Predictions are much more complicated when impaired bioavailability exists."	( Influence of bioavailability on the calculated Michaelis-Menten parameters of phenytoin in children. Brand, N; Koren, G; MacLeod, SM, 1984)	0.5
"Relative bioavailability (RB) of two commercially available phenytoin preparations showed greater differences in absorption in children than in adults."	( Relative bioavailability of two different phenytoin preparations. Evidence for an age dependency. Higashi, A; Ikeda, T; Matsuda, I; Matsukura, M, 1984)	0.77
"Several factors affecting the bioavailability of 5,5-diphenylhydantoin (I) and its sodium salt (I-Na) were examined in dogs in relation to meal and following results were obtained."	( Biopharmaceutical studies on hydantoin derivatives. IV. Factors affecting bioavailability of 5,5-diphenylhydantoin in dog. Fujioka, H; Tan, T, 1984)	0.27
" The therapeutic dose, clearance, extraction coefficient, bioavailability and half-life are the object of particular study."	( [Pharmacokinetics of anti-arrhythmics. 2. Clinical applications]. Bricaud, H; Lévy, RH; Lévy, S, 1980)	0.26
" Bioavailability from tablet formulation was rather poor (av 36% compared with that obtained with IV) and showed great variation between dogs."	( Clinical pharmacokinetics of phenytoin in the dog: a reevaluation. Frey, HH; Löscher, W, 1980)	0.55
"The Michaelis-Menten pharmacokinetics and bioavailability of phenytoin were evaluated in children."	( Plasma levels and pharmacokinetics of antipileptic drugs in children. Miura, H, 1981)	0.5
"The extent and rate of absorption of phenytoin (PHT) from tablet and powder were studied in four healthy adult volunteers."	( Bioavailability of phenytoin on single and multiple oral doses of two dosage forms in normal subjects. Isozaki, S; Kohda, Y; Nakagawa, F; Nishihara, K; Saitoh, Y; Tamura, Z, 1983)	0.87
" Because of these physicochemical properties, phenytoin is subject to erratic bioavailability in a variety of dosage forms both in its acidic as well as sodium salt forms."	( Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs. Roberts, RD; Stella, VJ; Yamaoka, Y, 1983)	0.9
" The products had been the subject of earlier in vivo bioavailability studies with human subjects."	( In vivo-in vitro correlations with a commercial dissolution simulator II: papaverine, phenytoin, and sulfisoxazole. Meyer, MC; Yau, MK, 1983)	0.49
" administration and was poorly absorbed with a bioavailability of 34."	( Pharmacokinetics of phenytoin (diphenylhydantoin) in horses. Beech, J; Kowalczyk, DF, 1983)	0.59
"Physico-chemical properties, dissolution profiles, and bioavailability of the molecular compound composed of equimolar amount of 1-benzenesulfonyl-5, 5-diphenylhydantoin (BSDH) and antipyrine were studied."	( Biopharmaceutical studies on hydantoin derivatives. III. Physico-chemical properties, dissolution behavior, and bioavailability of the molecular compound of 1-benzenesulfonyl-5,5-diphenylhydantoin and antipyrine. Fujioka, H; Tan, T, 1982)	0.26
" Dose-dependent changes in rate and extent of absorption, bioavailability (saturation of first-pass metabolism), distribution (saturation of protein binding sites) and metabolism are discussed."	( Pharmacokinetics of drug overdose. Benowitz, NL; Pond, S; Rosenberg, J, )	0.13
" 2 The bioavailability of phenytoin when given concomitantly with Asilone was decreased in five of six volunteer subjects (by greater than 30% in three subjects) although this decrease was not shown to be statistically significant."	( The effect of activated dimethicone and a proprietary antacid preparation containing this agent on the absorption of phenytoin. Collier, PS; McElnay, JC; Uprichard, G, 1982)	0.77
" Absolute bioavailability of IM PB was 101 +/- 11%."	( Kinetics of phenobarbital in normal subjects and epileptic patients. Comfort, CP; Friel, PN; Kaluzny, SP; Levy, RH; Wilensky, AJ, 1982)	0.26
"In connection with the function of a newly constructed absorption model the problem of interpretation of values obtained by models in regard of bioavailability is discussed."	( [Feasibility of the in vitro evaluation of bioavailability. 3: Method of operation of a newly-developed absorption model and results obtained with it]. Buchmann, E; Fuchs, G; Fürst, W; Neubert, R; Stütz, B, 1982)	0.26
"The bioavailability of phenytoin from rapid release capsule and oral solution formulations relative to that of a slow release capsule formulation was assessed in five patients who had participated in a three-way crossover study performed at steady state."	( Rapid and slow release phenytoin in epileptic patients at steady state: assessment of relative bioavailability utilizing Michaelis-Menten parameters. Gumnit, RJ; Leppik, IE; Pepin, SM; Sawchuk, RJ, 1982)	0.89
" The marked decrease in the estimated absorption rate constant between phases 1 and 2 for each drug may have been due to slow dissolution of a large congealed mass of phenytoin and primidone in the gut."	( Acute phenytoin and primidone intoxication: a pharmacokinetic analysis. Cloyd, JC; Matzke, GR; Sawchuk, RJ, )	0.81
" Inter- and intra-subject variation in bioavailability was small (0."	( Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics. Dumbrell, M; Khouw, V; Sandor, P; Sellers, EM, 1981)	0.52
" Bioavailability of Hct showed considerable intra- and interindividual variation (32--87% and 42--77% respectively), but phenytoin did not influence the disposition parameters of the diuretic."	( Disposition of hydrochlorothiazide (Hct) during phenytoin (Ph) treatment. Brennes, M; Hoppe-Seyler, G; Keller, E; Schollmeyer, P; Sulzer, U, 1981)	0.73
"Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally."	( Effect of antacids on phenytoin bioavailability. Carter, BL; Garnett, WR; Howell, JR; Pellock, JM; Stratton, MA, 1981)	0.76
"Subtherapeutic phenytoin serum levels and loss of seizure control occurred in a 31-year-old man due to decreased bioavailability of oral drug."	( Reduced seizure control due to spoiled phenytoin capsules. Cloyd, JC; Gumnit, RJ; Lesar, TS, 1980)	0.88
" Tablets containing phenytoin precipitated with polysorbate 80 showed faster in vitro dissolution and also higher bioavailability than tablets prepared with phenytoin free acid with different excipients."	( Effect of formulation on dissolution and bioavailability of phenytoin tablets. Belpaire, F; Chakrabarti, S; Moerman, E, 1980)	0.83
" We suggest that the interaction occurs at gastrointestinal level with a reduction of PHT and VPA oral bioavailability during antiviral treatment."	( Possible interaction between acyclovir and antiepileptic treatment. Parmeggiani, A; Posar, A; Riva, R; Rossi, PG, 1995)	0.29
" Second, the effect of magnesium/aluminium hydroxide on the relative bioavailability of nizatidine, famotidine, cimetidine and ranitidine was evaluated in healthy volunteers."	( Drug interactions of H2-receptor antagonists. Bachmann, KA; Jauregui, L; Levine, L; Miller, K; Reese, J; Sullivan, TJ, 1994)	0.29
" Bioavailability studies were carried out with both emulsions in Wistar male rats."	( Influence of the emulsion sign in phenytoin bioavailability. Fagiolino, P; Jelen, M; León, AS; Savio, EO, 1994)	0.57
"The bioavailability of capsules of phenytoin was determined by two methods: a method involving the numerical integration of the Michaelis-Menten equation and an alternative method involving fitting the time course of plasma concentrations, following the administration of the reference intravenous dosage, to an empirical quadratic function of time."	( Application of a simplified method to determine bioavailability of an oral dose of phenytoin. Begg, EJ; Davis, AL; Graham, GG; Kennedy, MC, 1993)	0.79
" The present study in 7 normal volunteers and 8 adult male patients with iron deficiency anaemia (IDA) was done to investigate the effect of iron deficiency and its treatment with total dose iron (TDI) on the bioavailability of a single dose of phenytoin."	( Effect of iron deficiency anaemia and its treatment on single dose phenytoin bioavailability. Acharya, VN; Joshi, MV; Kshirsasgar, NA; Mehta, BC; Pohujani, SM, 1993)	0.7
"The effect of a high-fat meal on the bioavailability of free acid phenytoin (DPH) from Hydantol powder with a large particle size (mean particle size, 190 microns) was investigated in four healthy male subjects."	( Effect of a high-fat meal on the bioavailability of phenytoin in a commercial powder with a large particle size. Hamaguchi, T; Irie, T; Iwamoto, B; Miyoshi, K; Mizuno, N; Morita, Y; Shinkuma, D; Yamanaka, Y, 1993)	0.77
"Measurement of the absolute bioavailability of phenytoin (PHT) derived from test doses of phenytoin prodrug (PPD) at therapeutic PHT serum concentrations is complicated by two problems: 1) the area under the serum concentration versus time curve (AUC) produced by a given size of test dose will vary directly with background PHT serum concentration due to the nonlinear pharmacokinetic properties of PHT; 2) PPD is more water soluble than PHT, making renal excretion of PPD more likely."	( Bioavailability studies of drugs with nonlinear pharmacokinetics: II. Absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by double-stable isotope technique. Browne, TR; Davoudi, H; Dougherty, CL; Evans, BA; Evans, JE; Kres, J; McEntegart, C; Miceli, JJ; Quon, C; Szabo, GK, 1993)	0.75
" Decreased phenytoin bioavailability may become more common with increased use of supplemental feeding tubes."	( Phenytoin malabsorption after jejunostomy tube delivery. Ray, TR; Rodman, DP; Stevenson, TL, )	1.96
"The bioavailability of phenytoin was evaluated in rats upon oral administration of phenytoin-lipid conjugates obtained by covalent binding of 3-hydroxymethylphenytoin to 1,3-dimyristoylglyceride via a succinidyl linkage, to 2-(1,3-dimyristoyl-2-glyceryl)butyric acid and to 3-myristoyloxy-2-methylpropionic acid."	( Bioavailability of phenytoin following oral administration of phenytoin-lipid conjugates to rats. Lambert, DM; Poupaert, JH; Scriba, GK, 1995)	0.93
" The absorption rate appears to be the rate-limiting step in the conversion of fosphenytoin to phenytoin after intramuscular administration (half-life range 22-41 min)."	( Fosphenytoin: a novel phenytoin prodrug. Boucher, BA, )	0.98
" However, the efficacy is lowered by the erratic bioavailability after oral administration."	( Bioavailability and anticonvulsant activity of 2-cyanoguanidinophenytoin, a structural analogue of phenytoin. Gallez, B; Geurts, M; Lambert, DM; Masereel, B; Scriba, GK, 1996)	0.53
"231/kg in a typical 42-kg patient, assuming that the bioavailability of orally administered phenytoin is 100%."	( Population pharmacokinetics of phenytoin in Japanese patients with epilepsy: analysis with a dose-dependent clearance model. Furusho, K; Hashimoto, Y; Hattori, H; Inui, K; Koue, T; Odani, A; Otsuki, Y; Takano, M; Takayanagi, K; Yasuhara, M, 1996)	0.8
" The unique properties of phenytoin such as poor water solubility and zero-order kinetics of its metabolism, together with difference in pharmaceutical formulations can result in dramatic changes in bioavailability of phenytoin capsule."	( Bioavailability of phenytoin sodium capsules available in Thailand. Part I: In vitro study. Payakachat, N; Suthisisang, C, 1998)	0.93
"Four phenytoin brands, dilantin and three local brands (brand A, B and C) were selected for the bioavailability study."	( Bioavailability of phenytoin sodium capsules available in Thailand. Part II: In vivo study. Chulavatnatol, S; Payakachat, N; Suthisisang, C; Towanabut, S, 1998)	1.14
" The relative bioavailability of fosphenytoin was 83%."	( Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin. Ebert, U; Löscher, W; Reissmüller, E, 1998)	0.87
"To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers receiving continuously infused enteral feedings."	( Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings. Altavela, JL; Doak, KK; Dunnigan, KJ; Haas, CE; Huntress, J; Reiser, JR; Reiss, RA, )	0.72
" There were no significant differences in bioavailability for PHT acid suspension and PHT sodium solution (0."	( Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings. Altavela, JL; Doak, KK; Dunnigan, KJ; Haas, CE; Huntress, J; Reiser, JR; Reiss, RA, )	0.46
"The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed."	( Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings. Altavela, JL; Doak, KK; Dunnigan, KJ; Haas, CE; Huntress, J; Reiser, JR; Reiss, RA, )	0.46
" Based on the hypothesis that these low melting prodrugs may have improved physical properties such as solubility and dissolution rate in gastrointestinal fluid, an enhanced bioavailability of these prodrugs may be observed relative to phenytoin."	( Some relationships between the physical properties of various 3-acyloxymethyl prodrugs of phenytoin to structure: potential in vivo performance implications. Martodihardjo, S; Rao, VM; Stella, VJ; Terada, K, 1998)	0.7
" When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site."	( Pediatric use of intravenous and intramuscular phenytoin: lessons learned. Wheless, JW, 1998)	0.83
" When dosed orally (25 mg/kg, DPH equivalent), the plasma levels of DPH converted from the prodrug were significantly higher and more sustained than those after DPH alone, giving bioavailability 11."	( Enhancement of the oral bioavailability of phenytoin by N-acetylation and absorptive characteristics. Iwaki, M; Kawaratani, D; Muraoka, O; Ogiso, T; Tanabe, G; Tanino, T, 1998)	0.56
" A male Caucasian who participated in six bioavailability studies in our laboratory over a period of several years showed extremely low clearance of two drugs: phenytoin and glipizide (both substrates of CYP2C9), but not for nifedipine (a CYP3A4 substrate) and chlorpheniramine (a CYP2D6 substrate)."	( Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Blaisdell, J; Dalton, JT; Goldstein, JA; Kidd, RS; Meyer, MC; Straughn, AB, 1999)	0.77
" The oral bioavailability of phenytoin after administration of phenytoin (1) and the selected prodrugs, 3-pentanoyloxymethyl 5, 5-diphenylhydantoin (2) and 3-octanoyloxymethyl 5, 5-diphenylhydantoin (3), in fed and fasted beagle dogs were compared to intravenously administered phenytoin."	( Aqueous solubility and dissolution rate does not adequately predict in vivo performance: a probe utilizing some N-acyloxymethyl phenytoin prodrugs. Martodihardjo, S; Rao, VM; Stella, VJ, 1999)	0.8
" Mean apparent bioavailability of the rectally administered phenytoin was 24."	( Absorption of rectally administered phenytoin: a pilot study. Chang, SW; da Silva, JH; Kuhl, DR, )	0.65
"The present study was undertaken to determine the effects of grapefruit juice (GFJ) on the oral bioavailability of phenytoin (DPH)."	( Lack of pharmacokinetic interaction between grapefruit juice and phenytoin in healthy male volunteers and epileptic patients. Garg, SK; Kumar, N; Prabhakar, S, 1999)	0.75
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."	( QSAR model for drug human oral bioavailability. Topliss, JG; Yoshida, F, 2000)	0.31
" The concepts of bioavailability and bioequivalence require further consideration."	( Is generic prescribing acceptable in epilepsy? Besag, FM, 2000)	0.31
"Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM)."	( Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses. DeToledo, J; Gidal, B; Morgan, RO; Pryor, FM; Ramsay, RE, 2001)	1.55
"8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F)."	( Disposition, elimination, and bioavailability of phenytoin and its major metabolite in horses. Birks, EK; Guan, F; Rudy, JA; Soma, LR; Teleis, DC; Tsang, DS; Uboh, CE; Watson, AO, 2001)	0.57
" The results suggest that co-administration of Mentat could improve the effectiveness of anti-epileptic drugs due to the increased bioavailability of the latter."	( Pharmacokinetic interactions of Mentat with carbamazepine and phenytoin. Gopumadhavan, S; Mitra, SK; Rafiq, M; Sundaram, R; Tripathi, M; Venkataranganna, MV, )	0.37
"The main objective of this study was to evaluate the influence of hydroxypropylated beta- and gamma-cyclodextrins and Me-beta-cyclodextrin (HP-beta-CD, HP-gamma-CD, and Me-beta-CD, respectively) on the dissolution rate and bioavailability of the antiepileptic agent, phenytoin (DPH)."	( Complexation of phenytoin with some hydrophilic cyclodextrins: effect on aqueous solubility, dissolution rate, and anticonvulsant activity in mice. Cutrignelli, A; Fanizzi, FP; Franco, M; Latrofa, A; Liso, G; Muggironi, M; Serra, M; Trapani, G, 2001)	0.84
"To determine inter-lot and intra-subject variability in the bioavailability of the 100 mg extended phenytoin sodium capsules."	( Variability in the bioavailability of phenytoin capsules in males and females. Chen, ML; Lesko, LJ; Meyer, MC; Mhatre, RM; Shah, VP; Straughn, AB; Williams, RL, 2001)	0.8
"There was very little difference in the bioavailability of the three lots of phenytoin."	( Variability in the bioavailability of phenytoin capsules in males and females. Chen, ML; Lesko, LJ; Meyer, MC; Mhatre, RM; Shah, VP; Straughn, AB; Williams, RL, 2001)	0.81
"Solid dispersions of phenytoin in polyethylene glycol 6000 and polyvinylpyrrolidone K-30 with different drug-to-carrier ratios were prepared by the solvent method with the aim of increasing dissolution rate and bioavailability of the drug."	( Dissolution properties and anticonvulsant activity of phenytoin-polyethylene glycol 6000 and -polyvinylpyrrolidone K-30 solid dispersions. Biggio, G; Franco, M; Latrofa, A; Liso, G; Muggironi, M; Provenzano, MR; Serra, M; Trapani, G; Tullio, C, 2001)	0.88
"Based on AUC(0-infinity), bioavailability of the Mylan product administered with food was 13% lower than that observed with Dilantin Kapseals."	( Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Cloyd, JC; Cook, J; Hietpas, TJ; Leppik, I; Randinitis, EJ; Wilder, BJ, 2001)	0.55
"The authors examined the effect of food on the bioavailability of Dilantin Kapseals in a nonblinded, single 100-mg dose, randomized, crossover trial."	( Effect of food on the bioavailability of 100-mg dilantin Kapseals. Cook, J; Randinitis, E; Wilder, BJ, 2001)	0.31
" Although its bioavailability is dependent on the formulation, bioequivalence is considered to be preserved between the three major formulations, of tablet, 97% fine granules, and 10% powder."	( [An increase in serum phenytoin concentration by changes of dosage form: case reports and its mechanism]. Mukai, S; Ohtani, H; Sawada, Y; Uotani, S; Yamaguchi, T, 2002)	0.63
" The bioavailability of the derived phenytoin relative to intravenous phenytoin is approximately 100% following intravenous or intramuscular administration."	( Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. Fischer, JH; Fischer, PA; Patel, TV, 2003)	1.22
"The objective of the study was to compare the bioavailability of a single oral 200-mg dose of four brands of phenytoin sodium available in the Indian market."	( A randomized, crossover, assessor-blind study of the bioequivalence of a single oral dose of 200 mg of four formulations of phenytoin sodium in healthy, normal Indian volunteers. Dalvi, SS; Gogtay, NJ; Gupta, AH; Jadhav, SP; Kirodian, BG; Kshirsagar, NA; Mhatre, RB, 2003)	0.74
" The bioavailability of these drugs differ among different pharmaceutical preparations and even for the same preparation."	( [Variance of bioavailability of pharmaceutical preparations and analysis of factors affecting it]. Hamaguchi, T; Mizuno, N; Shinkuma, D, 2003)	0.32
"The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investigated in 21 patients with epilepsy."	( Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability. Bartoli, A; Gatti, G; Marchiselli, R; Michelucci, R; Perucca, E; Pisani, F; Richens, A; Tassinari, CA; Timmings, P; Zaccara, G, 1993)	0.81
" In this study, it was found that a high fat diet increases the bioavailability of phenytoin and carbamazepine in New Zealand white rabbits."	( Influence of high fat diet (butter) on pharmacokinetics of phenytoin and carbamazepine. Garg, SK; Malhotra, S; Sidhu, S, 2004)	0.79
"Permeability of the blood-brain barrier is one of the factors determining the bioavailability of therapeutic drugs and resistance to chemically different antiepileptic drugs is a consequence of decreased intracerebral accumulation."	( RLIP76, a non-ABC transporter, and drug resistance in epilepsy. Awasthi, S; Awasthi, YC; Cucullo, L; Dini, G; Fazio, V; Hallene, KL; Janigro, D; Singhal, SS, 2005)	0.33
"Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers."	( Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy. Hota, D; Kharbanda, P; Pandhi, P; Pattanaik, S; Prabhakar, S, 2006)	0.78
"This study investigated the population pharmacokinetics and the enteral bioavailability of phenytoin (PTN) in neonates and infants with seizures."	( Application of routine monitoring data for determination of the population pharmacokinetics and enteral bioavailability of phenytoin in neonates and infants with seizures. Al Za'abi, M; Charles, B; Donovan, T; Lanner, A; Xiaonian, X, 2006)	0.76
" A number of medications either induce or inhibit this system which leads to changes in the bioavailability of the statins and the potential for either an increase in adverse effects or reduction in efficacy."	( Lipid lowering inefficacy of high-dose statin therapy due to concurrent use of phenytoin. Khandwala, HM, 2006)	0.56
" The effect of NIMO on hippocampal concentrations of PHT suggests that P-glycoprotein has a role in reduced central bioavailability of PHT in our epileptic refractory model."	( Nimodipine restores the altered hippocampal phenytoin pharmacokinetics in a refractory epileptic model. Auzmendi, J; Bramuglia, GF; Girardi, E; Gonzalez, NN; Höcht, C; Lazarowski, A; Opezzo, JA; Taira, CA, 2007)	0.6
"Interindividual variability in intestinal absorption and bioavailability might contribute to inadequate control of seizures under treatment with carbamazepine and phenytoin."	( Intestinal expression of cytochrome P450 enzymes and ABC transporters and carbamazepine and phenytoin disposition. Fried, M; Fritschy, JM; Kullak-Ublick, GA; Mueller, S; Pauli-Magnus, C; Simon, C; Stieger, B; Wieser, HG, 2007)	0.76
" Preliminary results from 60 patients on PHT therapy (41 elderly, mean age 76 years; 19 younger adults, mean age 41 years) indicate that PHT bioavailability did not differ between the two age groups; however, absorption and elimination half-lives were more variable in the elderly patients."	( Factors affecting antiepileptic drug pharmacokinetics in community-dwelling elderly. Birnbaum, AK; Cloyd, JC; Marino, S, 2007)	0.34
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."	( Hologram QSAR model for the prediction of human oral bioavailability. Andricopulo, AD; Moda, TL; Montanari, CA, 2007)	0.34
"To determine the effect of doses on the bioavailability of a prompt-release and an extended-release phenytoin capsule after given as single doses."	( Effect of doses on the bioavailability of phenytoin from a prompt-release and an extended-release preparation: single dose study. Chaichana, N; Chankrachang, S; Kumsorn, B; Rojanasthien, N; Sangdee, C; Teekachunhatean, S, 2007)	0.82
"The bioavailability of phenytoin from both preparations increased proportionally over the dose range of 100-300-mg, however, the bioavailability of the prompt-release preparation was higher than the corresponding doses of the extended-release product."	( Effect of doses on the bioavailability of phenytoin from a prompt-release and an extended-release preparation: single dose study. Chaichana, N; Chankrachang, S; Kumsorn, B; Rojanasthien, N; Sangdee, C; Teekachunhatean, S, 2007)	0.91
"The aim of this study is to develop and characterize a self-emulsifying drug delivery system (SEDDS) of phenytoin, and to compare its relative bioavailability to a commercially available suspension."	( Formulation and in vitro and in vivo characterization of a phenytoin self-emulsifying drug delivery system (SEDDS). Atef, E; Belmonte, AA, 2008)	0.8
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
" To show the importance of physicochemical properties, the classic QSAR and CoMFA of neonicotinoids and prediction of bioavailability of pesticides in terms of membrane permeability in comparison with drugs are described."	( Importance of physicochemical properties for the design of new pesticides. Akamatsu, M, 2011)	0.37
"We determined PHT bioavailability during steady-state therapy by 1) measurement of the two principal deconjugated PHT urinary metabolites, 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin (DHD); and 2) direct determination of absolute bioavailability after simultaneous administration of an oral formulation and parenteral stable-labeled PHT (SL-PHT)."	( Excretion of the principal urinary metabolites of phenytoin and absolute oral bioavailability determined by use of a stable isotope in patients with epilepsy. Aliwarga, T; Brundage, RC; Cloyd, JC; Goel, V; Leppik, IE; Marino, SE; Remmel, RP, 2011)	0.62
" Absolute bioavailability was 86."	( Excretion of the principal urinary metabolites of phenytoin and absolute oral bioavailability determined by use of a stable isotope in patients with epilepsy. Aliwarga, T; Brundage, RC; Cloyd, JC; Goel, V; Leppik, IE; Marino, SE; Remmel, RP, 2011)	0.62
" When PK parameters were grouped as low-medium-high, clearance, volume of distribution, half life and bioavailability were similar between discrete and cassette analysis for 90%, 86%, 95% and 90% of the total number of compounds tested, respectively."	( High-throughput analysis of standardized pharmacokinetic studies in the rat using sample pooling and UPLC-MS/MS. Betnér, I; Briem, S; Bueters, T; Dahlström, J; Kvalvågnaes, K, 2011)	0.37
"The aim of the present study was to evaluate the suitability of saliva as a biological fluid in relative bioavailability (RBA) studies, with the focus on the statistical design and data variability."	( Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 x 2 replicate crossover design. de Buschiazzo, PM; Fagiolino, P; Ruiz, ME; Volonté, MG, 2011)	0.37
"This study showed that phenytoin has an important effect on the pharmacokinetics of ivabradine in healthy subjects, reducing its bioavailability by approximately 70%."	( Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects. Leucuta, SE; Muntean, D; Neag, M; Popa, A; Vlase, L, 2012)	0.94
"Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern."	( Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration. Chen, SC; Dolton, MJ; McLachlan, AJ; Ng, K; Pont, L; Ray, JE, 2012)	0.38
"To compare and evaluate the bioavailability for intravenous fosphenytoin sodium with that of intravenous phenytoin sodium in Japanese subjects."	( Bioavailability of intravenous fosphenytoin sodium in healthy Japanese volunteers. Hiroki, T; Inoue, Y; Kobayashi, S; Shimasaki, S; Shimizu, K; Usui, N, 2013)	0.91
" Recent advancement in bioavailability enhancement of drugs by compounds of herbal origin has produced a revolutionary shift in the way of therapeutics."	( A comprehensive review on pharmacotherapeutics of herbal bioenhancers. Awale, MM; Chauhan, BN; Dudhatra, GB; Kamani, DR; Kumar, A; Modi, CM; Mody, SK; Patel, HB, 2012)	0.38
" Gender differences were also observed for CBZ-10,11-epoxide concentration, being bioavailability the main parameter responsible for this difference."	( Usefulness of salivary drug monitoring for detecting efflux transporter overexpression. Fagiolino, P; Lazarowski, A; Maldonado, C; Orozco-Suárez, S; Ruiz, ME; Vázquez, M; Volonté, MG, 2013)	0.39
" Both CBZ and PHT would modify their bioavailability and clearance by inducing efflux transporter throughout chronic treatments, from the first dose to multiple dose administration."	( Usefulness of salivary drug monitoring for detecting efflux transporter overexpression. Fagiolino, P; Lazarowski, A; Maldonado, C; Orozco-Suárez, S; Ruiz, ME; Vázquez, M; Volonté, MG, 2013)	0.39
" P-gp polymorphisms may also affect phenytoin efficacy by altering its bioavailability (F)."	( Studies on pharmacokinetic mechanism of phenytoin resistance in refractory epilepsy. Huang, JD; Huang, YS; Lai, ML; Tien, YE, 2013)	0.93
"In the pharmaceutical industry, salt is commonly used to improve the oral bioavailability of poorly soluble compounds."	( Incorporation of physiologically based pharmacokinetic modeling in the evaluation of solubility requirements for the salt selection process: a case study using phenytoin. Chiang, PC; Wong, H, 2013)	0.59
"Given the increasing number of poorly soluble and thus poorly bioavailable active pharmaceutical materials, there is a demand for innovative formulation platforms for such molecules."	( Particular film formation of phenytoin at silica surfaces. Baumgartner, R; Roblegg, E; Werzer, O; Zawodzki, M, 2014)	0.69
" Posaconazole relative bioavailability was 55% lower in patients who received posaconazole than in healthy volunteers."	( Understanding variability in posaconazole exposure using an integrated population pharmacokinetic analysis. Brüggemann, RJ; Burger, DM; Dolton, MJ; McLachlan, AJ, 2014)	0.4
" There may be a large difference of bioavailability among the generic drugs that especially have a narrow therapeutic index, and this may affect clinical outcomes."	( Switching between phenytoin generics in patients with epilepsy may lead to increased risk of breakthrough seizure: chart analysis and practice recommendations. Chu, K; Jung, KH; Lee, SK; Lee, ST; Moon, J; Shin, JW, 2014)	0.74
"We confirmed that there was a significant difference in bioavailability between generic phenytoin."	( Switching between phenytoin generics in patients with epilepsy may lead to increased risk of breakthrough seizure: chart analysis and practice recommendations. Chu, K; Jung, KH; Lee, SK; Lee, ST; Moon, J; Shin, JW, 2014)	0.96
" In order to evaluate the oral bioavailability of PHT, two groups were administered with oral or intraperitoneal doses of 100mg/kg and plasma level were measured."	( Chronic administration of phenytoin induces efflux transporter overexpression in rats. Alvariza, S; Fagiolino, P; Feria-Romero, I; Orozco-Suárez, S; Vázquez, M, 2014)	0.7
" In phase IV screening, the bioavailability of active compounds was assessed on oral administration."	( Preliminary anticonvulsant and toxicity screening of substituted benzylidenehydrazinyl-N-(6-substituted benzo[d]thiazol-2-yl)propanamides. Ali, R; Siddiqui, N, 2014)	0.4
"To describe the pharmacokinetics of fosphenytoin (FPHT) sodium injection when administered orally, and to determine the relative oral bioavailability (FREL ) of FPHT sodium injection compared with PHT sodium injection based on pharmacokinetic modeling in healthy volunteers."	( Relative bioavailability of orally administered fosphenytoin sodium injection compared with phenytoin sodium injection in healthy volunteers. Acquisto, NM; Forrest, A; Haas, CE; Huntress, JD; Kaucher, KA; Kaufman, DC; Rao, GG, 2015)	0.94
" Its maximal plasma concentration is achieved within 90-190 min following intramuscular administration with bioavailability being complete after intravenous injection."	( The safety and efficacy of fosphenytoin for the treatment of status epilepticus. Borowicz, KK; Czuczwar, SJ; Popławska, M, 2015)	0.71
"Water-soluble prodrug strategy is a practical alternative for improving the drug bioavailability of sparingly-soluble drugs with reduced drug efficacy."	( Novel prodrugs with a spontaneous cleavable guanidine moiety. Hamada, Y, 2016)	0.43
" After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T)."	( Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer. Hashimoto, N; Mori, H; Nishimura, Y; Tachibana, S; Takatsuka, T; Yuminoki, K, 2016)	0.7
" We studied whether glucocorticoid receptor (GR) silencing or inhibition in human epileptic brain endothelial cells (EPI-ECs) functionally impacts drug bioavailability across an in vitro model of the blood-brain barrier (BBB) by CYP-multidrug transporter (multidrug resistance protein 1, MDR1) mechanisms."	( Modulation of glucocorticoid receptor in human epileptic endothelial cells impacts drug biotransformation in an in vitro blood-brain barrier model. Bingaman, W; Ghosh, C; Gonzalez-Martinez, J; Hossain, M; Janigro, D; Khan, S; Marchi, N; Mishra, S; Najm, I, 2018)	0.48
" In both scenarios, hypothetical phenytoin capsules with different formulation-related PK parameters, such as relative bioavailability and absorption rates, were included in the simulations."	( Is Bioequivalence Established Based on the Reference-Scaled Average Bioequivalence Approach Relevant to Chronic Administration of Phenytoin? Perspectives Based on Population Pharmacokinetic Modeling and Simulations. Fang, L; Kim, H; Lesko, LJ; Meng, Z; Schmidt, S; Trame, MN; Yu, J; Zhao, L, 2019)	1
"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
" In conclusion, the use of phosphate ester prodrugs could be an efficient and safe strategy to increase the intranasal bioavailability of poorly soluble drugs."	( Intranasal fosphenytoin: The promise of phosphate esters in nose-to-brain delivery of poorly soluble drugs. Alves, G; Pires, PC; Rodrigues, M; Santos, AO; Santos, LT, 2021)	0.98
" In a previous study, the intranasal administration of aqueous-based formulations of fosphenytoin led to high but delayed phenytoin bioavailability compared to the intravenous route."	( Nose-to-brain delivery of phenytoin and its hydrophilic prodrug fosphenytoin combined in a microemulsion - formulation development and in vivo pharmacokinetics. Alves, G; Fazendeiro, AC; Pires, PC; Rodrigues, M; Santos, AO, 2021)	1.14
"Many lead compounds fail to reach clinical trials despite being potent because of low bioavailability attributed to their insufficient solubility making solubility a primary and crucial factor in early phase drug discovery."	( Structural modification aimed for improving solubility of lead compounds in early phase drug discovery. Baidya, ATK; Das, B; Kumar, R; Mathew, AT; Yadav, AK, 2022)	0.72

Dosage Studied

Among Chinese epileptic patients, the saturation of phenytoin metabolism occurs at the dosage of 4 mg/kg/day. Clinicians should be aware of this potential drug-nutrient interaction and design a patient-specific care plan.

Excerpt	Relevance	Reference
" The one statistically significant interaction found was that in which phenytoin dosage decreased plasma carbamazepine concentrations."	( Interactions between anticonvulsants. Eadie, MJ; Lander, CM; Tyrer, JH, 1975)	0.49
"A simple, specific GLC procedure is described for the analysis of one sedative and six anticonvulsant drugs in pharmaceutical dosage forms."	( Simple GLC analysis of anticonvulsant drugs in commercial dosage forms. Lawrence, RC; Lovering, EG; Watson, JR, 1978)	0.26
"Outpatient prescriptions dispensed to 17,000 individuals in the county of Jämtland, Sweden, have been analyzed with regard to doses and dosage schedules."	( Doses and dosage intervals of drugs--clinical practice and pharmacokinetic principles. Boëthius, G; Sjöqvist, F, 1978)	0.26
"Steady-state serum-phenytoin levels were measured in five patients whose phenytoin dosage was changed three or more times for therapeutic purposes."	( Serum-phenytoin levels in management of epilepsy. Dunlop, A; Richens, A, 1975)	1.06
" No alteration of plasma half-life of warfarin, phenytoin, or tolbutamide was observed following dosage with the tricyclic antidepressants used."	( Effects of tricyclic antidepressants on drug metabolism. Birkett, DJ; Graham, GG; Pond, SM; Wade, DN, 1975)	0.51
" The three brands tested were equivalent as to their bioavailability with respect to plasma concentrations during one dosing interval, the area under the plasma level time curve, the time of peak plasma concentration, and the urinary excretion of the primary metabolite."	( The bioavailability of phenytoin. Eichelbaum, M; Fröscher, W; Gugler, R; Hildenbrand, G, 1977)	0.57
" Phenytoin dosage was increased to study the effect on the frequency of seizures and the serum concentrations of phenytoin and phenobarbitone."	( Therapeutic and pharmacokinetic effects of increasing phenytoin in chronic epileptics on multiple drug therapy. Johnson, RH; Lambie, DG; Nanda, RN; Shakir, RA, 1976)	1.41
" The results were used to calculate the plasma levels of phenytoin in relation to dosage and to measure the effect of the simultaneous use of phenobarbital on the phenytoin plasma levels and of primidone together with phenobarbital on phenytoin concentration."	( In vivo interaction of anticonvulsant drugs. The mathematical correlation of plasma levels of anticonvulsant drugs in epileptic patients. Abarbanel, J; Eylath, U; Herishanu, Y; Rosenberg, P, 1978)	0.5
"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
" The physiologic explanations for the necessary phenytoin dosage adjustment in infants weighing less than 20 kg are discussed."	( Increased doses of phenytoin for infants. Cady, WJ; Rapp, RP; Young, AB, 1978)	0.84
"Phenytoin serum concentrations in 115 epileptics treated on an inpatient basis showed, in two groups, only relatively weak correlation with the dosage used."	( [Clinical significance of serum phenytoin level]. Oettinger, B; Richter, K, 1978)	1.98
"The optimal dosage of phenytoin can be accurately determined by a pharmacokinetic method."	( Rapid metabolism of phenytoin: a method of calculating proper dosage. Allen, JP; Hawkins, DW; Hoffman, SF; Ludden, TM, 1979)	0.9
" Maintenance dosage adjustments, when necessary, are based on serial plasma concentrations of the drug."	( Posttraumatic epilepsy prophylaxis. Brooks, WH; Madauss, W; Norton, JA; Rapp, R; Young, B, 1979)	0.26
" It was found that: (1) a single dose of phenytoin suspension or capsules (5mg/kg/day) produced inadequate serum levels 16 and 24 hours after ingestion, and for this reason single dosage is not recommended; (2) twice-daily dosage of phenytoin suspension or capsules (5mg/kg/day) produced adequate serum levels in most children throughout the 24 hours, and this dosage is recommended; (3) 12 children continued to have seizures but when the dose was increased to 10mg/kg/day six of the 12 obtained control of seizures; (4) phenytoin reached equilibrium in the serum in five days provided the child had not previously been taking phenobarbitone; (5) of 13 children who had been taking phenobarbitone, 10 did not achieve equilibrium of phenytoin in serum for one to four weeks; (6) phenytoin suspension given twice-daily produced satisfactory serum levels provided the bottle was shaken well before dispensing; (7) apart from minor variations, phenytoin maintained its level in serum during the 14 to 30 months follow-up period, whether 5mg or 10mg/kg/day of phenytoin was given."	( Phenytoin serum levels in children with epilepsy: a micro immuno-assay technique. Broughton, PM; Forsythe, WI; Prendergast, MP; Toothill, C, 1979)	1.97
" Plasma DPH levels of more than 10 mug/ml were achieved within 16 to 38 hr in the children given loading doses and within 5 days in the conventionally dosed children."	( Loading and conventional dose therapy with phenytoin in children: kinetic profile of parent drug and main metabolite in plasma. Höjer, B; Rane, A; Wilson, JT, 1976)	0.52
" Treatment with 25 OH CC in high dosage brought about clinical, radiological and laboratory cure of osteomalacia in both cases, reducing the frequency of fits in the epileptic patient."	( [4 cases of osteomalacia during anticonvulsant or sedative treatment]. Alcalay, M; Amor, B; Bontoux, D; Cayla, J; Charbonnier, A; Mery, C; Miravet, L; Rondier, J, 1975)	0.25
" The "specific" use of each drug on the various forms of epileptic seizures is determined and the possibility of crisis control with reduction of the drugs dosage is verified."	( [Effect of drugs on electroclinical types of epileptic seizures in Lennox-Gastaut syndrome]. Lison, MP; Speciali, GG, 1977)	0.26
" Commonly used drugs are discussed and the effects of disease, drug dosage and hypoalbuminaemia on drug-protein binding are reviewed."	( Protein binding of drugs--the clinical significance. Buchanan, N, 1978)	0.26
" Therefore, the dose range compatible with a therapeutic serum concentration is narrow within subjects, and monitoring serum concentrations is of particular value in dosage tailoring."	( Clinical pharmacokinetics of phenytoin. Richens, A, )	0.42
" Schedules of dosage for phenytoin whould be appropriately adjusted to compensate for this clinically important interaction of drugs."	( Clinical importance of the interaction of phenytoin and isoniazid: a report from the Boston Collaborative Drug Surveillance Program. Greenblatt, DJ; Miller, RR; Porter, J, 1979)	0.83
" Phenytoin dosage was increased to improve seizure control but produced relatively low blood levels during pregnancy."	( Epilepsy and pregnancy. Serum thyroxine levels during phenytoin therapy. Ramsay, RE; Spellacy, WN; Strauss, RG; Wilder, BJ; Willmore, LJ, 1979)	1.42
" Subjects were on 2 or 3 different dosing rates from 260 to 600 mg phenytoin sodium daily."	( Phenytoin cumulation kinetics. Allen, JP; Burrow, SR; Clementi, WA; Ludden, TM; Stavchansky, SA, 1979)	1.94
" The majority of the patients receiving Comital-L tablets showed low serum levels of phenytoin and high serum levels of phenobarbital, while patients treated with the usual daily dosage of Hydantol-F tablets showed adequate therapeutic serum levels of both phenytoin and phenobarbital."	( Serum levels of phenytoin and phenobarbital in epileptic patients treated with mixture antiepileptic tablets, Comital-L or Hydantol-F. Hattori, M; Kazamatsuri, H, 1979)	0.83
"The effect of dosage schedules on plasma drug levels was evaluated in two groups of ambulant epileptic patients, whose treatment with diphenylhydantoin (DPH) or phenobarbital (PB) had been simplified by reducing the daily frequency of the dosage regimens."	( Effectiveness of simplified dosage schedules on the management of ambulant epileptic patients. Galli, A; Zaccara, G, 1979)	0.26
"Model-dependent relationships describing the effects of absorption rate and dosing interval on steady-state phenytoin plasma concentrations are presented and discussed."	( Steady-state plasma concentrations as a function of the absorption rate and dosing interval for drugs exhibiting concentration-dependent clearance: consequences for phenytoin therapy. Rector, TS; Sawchuk, RJ, 1979)	0.67
"For the therapy of disturbances of the cardiac rhythm with phenytoin 3 different dosage regimes are examined, in which cases an oral application of phenytoin proves as not suitable."	( [Serum level determination in patients with acute myocardial infarction under diphenylhydantoin therapy]. Kettner, W; Quednow, B; Walther, H; Wilckens, H, 1979)	0.5
" The animals were made physically dependent by 5 weeks of twice daily "maximally tolerable" sodium pentobarbital dosing intragastrically."	( Evaluation of anticonvulsants in barbiturate withdrawal. Boisse, NR; Okamoto, M; Rosenberg, HC, 1977)	0.26
" Enzyme induction in connection with low phenytoin dosage and inhibition by high dosage is the suggested mechanism."	( The effect of phenytoin on the tissue concentrations of digoxin in the rat. Allonen, H, 1977)	0.88
"Acute dose-response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens."	( Epileptiform seizures in domestic fowl. VII. Plasma phenytoin concentrations and anticonvulsant activity. Crawford, RD; Davis, HL; Johnson, DD, 1978)	0.79
"Ambulant patients with recently diagnosed generalised or psychomotor seizure disorders or both were randomly assigned to two dosage regimens of phenytoin."	( Phenytoin dosage in ambulant epileptic patients. Alberts, M; Terrence, C, 1978)	1.9
" Although phenytoin dosage remained relatively constant, plasma phenytoin concentrations during pregnancy were significantly lower than nonpregnant concentrations."	( Hematologic effects of phenytoin therapy during pregnancy. Ramsay, RE; Strauss, RG; Wilder, BJ; Willmore, LJ, 1978)	0.97
" Mean saliva phenytoin concentrations did not differ significantly between the two treatment settings and were low largely because of the low mean dosage prescribed."	( Compliance with anticonvulsant therapy in a hospital clinic and in the community. Dollery, CT; Mucklow, JC, 1978)	0.63
" When clinically indicated the daily dosage rate was adjusted by 50 mg steps until a serum concentration of 10--20 mg/l was produced."	( Individual variation in daily dosage requirements for phenytoin sodium in patients with epilepsy. Barot, MH; Grant, RH; Maheendran, KK; Mawer, GE; Woodcock, BG, 1978)	0.51
" Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen."	( Kinetics of drug interactions in the treatment of epilepsy. Guelen, P; Knop, H; Schobten, F; van der Kleijn, E; Vree, T; Westenberg, H, 1978)	0.26
"A case is presented of fetal teratogenic damage from an unusually high maternal dosage of diphenylhydantoin, 600 mg daily, to a 40-kg woman throughout pregnancy."	( Diphenylhydantoin teratogenicity in man. Chang, MJ; Chi, CC; Tsai, CJ; Yang, TS, 1978)	0.26
" The nystagmus disappeared when phenytoin dosage was reduced."	( Downbeat nystagmus due to anticonvulsant toxicity. Alpert, JN, 1978)	0.54
" Consequently, serum content after single or repeated oral dosage of 10 mg/kg of body weight did not exceed a concentration of 2 microgram/ml."	( Serum concentrations of orally administered diphenylhydantoin in dogs. Sanders, JE; Yeary, RA, 1978)	0.26
" The data indicate that the dosage regimen described is suitable for patients on oral phenytoin who have to be transferred to im drug for short periods."	( Oral and intramuscular phenytoin. Ramsay, RE; Wilder, BJ, 1976)	0.79
" The initial dosage of 6 mg/kg DPH or 15 mg/kg CARB was corrected according to the serum values aiming at therapeutic intervals of 8-16 mg/1 DPH and 6-10 mg/1 CARB."	( A comparative controlled study between carbamazepine and diphenylhydantoin in psychomotor epilepsy. Kühl, V; Lund, M; Olsen, PZ; Simonsen, N; Wendelboe, J, 1976)	0.26
" As a consequence, shorter dosing intervals of these drugs seems to be advisable, rather than a reduction in the total daily dose."	( Drug protein binding and the nephrotic syndrome. Azarnoff, DL; Gugler, R, 1976)	0.26
" Combined treatment with other anticonvulsant drugs decreases the half-life and more frequent dosing may be necessary."	( Clinical pharmacokinetics of anticonvulsants. Dam, M; Hvidberg, EF, 1976)	0.26
" (3) Use of well-standardized, yet simplified, mental performance tests in combination with changes in the dosage of medication can help in reaching a compromise between acceptable seizure control and avoidance of excessive slowing of mental activity."	( Effects of different dosages of anticonvulsant drugs on mental performance in patients with chronic epilepsy. Dekaban, AS; Lehman, EJ, 1975)	0.25
"This study was undertaken to determine the relationship of serum ACD levels to dosage in a group of patients who had been seizure free for at least two years."	( The relation of anticonvulsant drug levels to complete seizure control. Feldman, RG; Pippenger, CE, 1976)	0.26
"A parenteral dosing regimen was designed for the immediate attainment and maintenance of therapeutic plasma levels of phenytoin in patients requiring anticonvulsant therapy, but not able to tolerate oral medication."	( Maintenance of therapeutic phenytoin plasma levels via intramuscular administration. Cady, W; Hackman, J; Kostenbauder, H; Pancorbo, S; Perrier, D; Rapp, R; Young, B, 1976)	0.76
"The present study investigated order and temporal spacing interactions of phenytoin and phenobarbital in terms of plasma levels during multiple dosing in monkeys."	( Interactions of phenytoin and phenobarbital in terms of order and temporal spacing of administration in monkeys. Farquhar, JS; Levy, RH; Lockard, JS; Uhlir, V, 1976)	0.83
"Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients."	( Individualization of phenytoin dosage regimens. Allen, JP; Hoffman, SF; Lalka, D; Ludden, TM; McNay, JL; Nappi, JM; Valutsky, WA; Vicuna, AV; Wallace, JE, 1977)	0.83
" Dosage adjustments of DPH in patients were not associated with major changes in the plasma level of unconjugated 4-OH-DPH."	( Plasma concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin in phenytoin-treated patients. Garle, M; Hoppel, C; Rane, A; Sjöqvist, F, 1977)	0.49
"A digital computer curve-fitting method, designed to estimate pharmacokinetic model constants by utilizing all drug concentration-time data collected during repetitive dosing studies, was applied to data manifesting systematic dose-to-dose variability in one or another of the pharmacokinetic parameters."	( Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration. Colburn, WA; Gibaldi, M, 1977)	0.26
" During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data."	( Pharmacokinetic observations of phenytoin disposition in the newborn and young infant. Aranda, JV; Greenwald, A; Loughnan, PM; Neims, AH; Purton, WW; Watters, G, 1977)	0.54
" The low dosage of PB had no effect on SEPs except those recorded in the mesencephalic reticular formation; high dosage resulted in general SEP attenuation."	( Phenobarbital and phenytoin effects on somatosensory evoked potentials and spontaneous EEG in normal cat brain. Kaplan, BJ, 1977)	0.59
" Despite adequate oral dosage of DPH (5 mg/kg/daily) the plasma level was very low (2."	( Phenytoin encephalopathy as probable idiosyncratic reaction: case report. Ambrosetto, G; Baruzzi, A; Lugaresi, E; Tassinari, CA, 1977)	1.7
" There was a significant progressive loss of GABA with increasing dosage of DPH."	( Effect of diphenylhydantoin on gamma aminobutyric acid (GABA) and succinate activity in rat Purkinje cells. Gabra-Sanders, T; Hitchcock, E, 1977)	0.26
" The long half-life in adults makes single daily dosing realistic in terms of blood levels and anticonvulsant effectiveness."	( Phenytoin kinetics in children. Carter, DE; Curless, RG; Walson, PD, 1976)	1.7
"A 28-year-old male of progressive myoclonus epilepsy was reported, who had showed a gradual progression in myoclonus, mental retardation and cerebellar symptoms, and had been treated with a large dosage of diphenylhydantoin."	( A neuropathological case-study of myoclonus epilepsy. Ikeda, K; Ikeda, S; Namba, M; Nishikubo, M; Yoshimura, T, 1976)	0.26
" prescribing too low a dosage (the average dose in the adult is 5 mg/kg/day) or lack of cooperation by the patient who either takes the drug irregularly or fails to take it at all."	( [Determination of plasma phenytoine and treatment of epileptics]. De Crousaz, G, 1976)	0.56
"Motor nerve conduction velocity was measured after dosing guinea-pigs with 200-400 μmol/kg diphenylhydantoin (DPH) daily for three to four days."	( Acute conduction velocity changes in guinea-pigs after administration of diphenylhydantoin. Goldberg, V; Le Quesne, PM; Vajda, F, 1976)	0.26
"Phenytoin was given in full dosage to eight patients with thalamic pain and two others with intractable pain resistant to other forms of treatment."	( A brief trial of phenytoin therapy for thalamic pain. Agnew, DC; Goldberg, VD, 1976)	2.04
" Subtherapeutic levels appear to be due to inadequate dosage adjustment."	( The necessity of drug level monitoring in anticonvulsant drug therapy. Bailey, DG; Davis, HL; Johnson, GE; Wilson, TW, 1976)	0.26
" Although plasma concentrations significantly correlate with the administered dose, predictability of plasma levels in the individual patients given fixed dosage schedules is strongly limited by large interindividual variability."	( [Epidemiological observations on plasma levels of diphenylhydantoin in 130 patients on prolonged treatment (author's tranls)]. Calzetti, S; Frigo, GM; Gatti, G; Perucca, E; Poloni, M; Teggia-Droghi, M; Visintini, D, )	0.13
" The dosage of DPH (Dilantin) was 100 mg twice daily, and placebo capsuales of identical appearance were given on the same schedule."	( Effects of diphenylhydantoin on mental abilities in the elderly. Lowrey, JB; Smith, WL, 1975)	0.25
" It is proposed that this model will be useful in the selection of an appropriate dosing regimen in situations in which intramuscular administration of phenytoin is indicated."	( Bioavailability and single-dose pharmacokinetics of intramuscular phenytoin. Blacker, HM; Foster, TS; Hulon, WC; Kinkel, AW; Kostenbauder, HB; McGovren, JP; Perrier, DG; Rapp, RP, 1975)	0.69
" Unit dose packaging is used because the oral solid dosage forms (including placebos) are made to look alike."	( Drug use and distribution in a pain rehabilitation center. Beckner, TF; Idsvoog, P, 1975)	0.25
" Clinical and laboratory observations including plasma durg concentrations, still provide the best means for adjusting dosage regimens in patients with fluctuating hepatic function."	( Influence of acute viral hepatitis on phenytoin kinetics and protein binding. Blaschke, TF; Meffin, PJ; Melmon, KL; Rowland, M, 1975)	0.53
" However, in these patients it was not necessary to diminish the dosage since the absolute concentration of unbond drug was unchanged due to a compensatory increase in the apparent volume of distribution and plasma clearance."	( Diphenylhydantoin: correlation between protein binding and albumin concentration. Azarnoff, DL; Gugler, R; Shoeman, DW, 1975)	0.25
" Simultaneous administration of imipramine and pentobarbital at the same dosage as in male rats is lethal for female rats without bile fistula within 30 min."	( Biotransformation and biliary excretion of imipramine in rats under various experimental conditions. Gigon, PL, 1975)	0.25
" The presence of immunological defects was independent of the dosage of drug, its serum concentration, the duration of therapy and the sex of the subject."	( Depression of immune competence by phenytoin and carbamazepine. Studies in vivo and in vitro. Forbes, IJ; Sorrell, TC, 1975)	0.53
" The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57."	( Phenytoin: pharmacokinetics and bioavailability. Azarnoff, DL; Gugler, R; Manion, CV, 1976)	1.7
" It is concluded that no modifications of phenytoin dosage are necessary in elderly people."	( [Phenytoin pharmacokinetics in young and older adults]. Estruch, J; Galdames, D; Martinetti, A; Saavedra, I, 1992)	1.46
" On the basis of these considerations and clinical reports describing the use of these drugs, we make dosage recommendations to enable the practitioner to individualize therapeutic regimens."	( Drugs used in the management of trigeminal neuralgia. Patsalos, PN; Zakrzewska, JM, 1992)	0.28
" The usual phenytoin (PHT) dosage in adults is 4-6 mg/kg per day, but children may need a dosage three to five times higher."	( Metabolism of antiepileptic medication: newborn to elderly. Leppik, IE, 1992)	0.67
"Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine."	( Bioavailability and bioinequivalence of drug formulations in small animals. Watson, AD, 1992)	0.28
"To report unusually high theophylline dosing requirements in a smoker receiving concomitant therapy with phenytoin and phenobarbital."	( Massive theophylline dosing in a heavy smoker receiving both phenytoin and phenobarbital. Basile, SA; Cury, JD; Nicholson, JP, 1992)	0.74
"The additive influence of smoking, phenytoin, and phenobarbital greatly increased the theophylline dosing requirements."	( Massive theophylline dosing in a heavy smoker receiving both phenytoin and phenobarbital. Basile, SA; Cury, JD; Nicholson, JP, 1992)	0.8
" Regular 2 weekly follow up for a minimum period of 2 months was done, after altering the drug dosage and bringing plasma level(s) within therapeutic range."	( "An analysis of epileptic patients nonresponsive to drugs". Joshi, MV; Karande, SC; Kshirsagar, NA; Shah, PU, 1992)	0.28
" There was no calcitonin correlation with the anticonvulsant dosage or with the total doses ingested."	( Long-term influence of anticonvulsant agents on calcitonin, parathyroid hormone and osteocalcin. Arias, JA; Cabranes, JA; Rico, H; Varela de Seijas, E, 1992)	0.28
" It is demonstrated that an statistically significant pharmacokinetic interaction was found only after multiple dosing under conditions of steady-state, whereas after single dosing no interaction was observed."	( The importance of prospective planning of pharmacokinetic trials. Considerations of studies on the phenytoin-digoxin-(P-D) and phenytoin-digitoxin-(P-DT) interaction. Rameis, H, 1992)	0.5
" For corticosterone determinations, mice were dosed on GD 10, and blood was collected at 1, 4, 24, or 48 hr after dosing."	( The effect of teratogens on maternal corticosterone levels and cleft incidence in A/J mice. Hansen, DK; Holson, RR; Sheehan, DM; Sullivan-Jones, P, )	0.13
" Pharmacokinetic dose prediction methods have been developed allowing individual dosage adaptation."	( Therapeutic drug monitoring and pharmacokinetic dose prediction methods. Oellerich, M, 1992)	0.28
" The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants."	( Results of the multicenter evaluation of the CEDIA Phenytoin assay. Collinsworth, W; Courbe, A; Fuentes-Arderiu, X; Graham, J; Hannak, D; Hänseler, E; Kattermann, R; Klein, G; Knoke, A; Lehmann, P, 1992)	0.54
" Plasmapheresis did not significantly alter the serum concentration of phenytoin; dosage adjustments of phenytoin are therefore unnecessary."	( Removal of phenytoin by plasmapheresis in a patient with thrombotic thrombocytopenia purpura. Baker, DK; Hurwitz, CA; Tobias, JD, 1992)	0.91
" Previous work had demonstrated that PHT treatment significantly increased endogenous maternal corticosterone concentrations for approximately 48 hr after dosing in A/J mice."	( Embryotoxicity of phenytoin in adrenalectomized CD-1 mice. Branham, WS; Hansen, DK; Holson, RR; Sheehan, DM, 1992)	0.62
" Dose-response relationships with phenytoin supported the hypothesis that the voltage dependence of tonic block resulted from the higher affinity of the drugs for inactivated than for resting channels."	( Frequency and voltage-dependent inhibition of type IIA Na+ channels, expressed in a mammalian cell line, by local anesthetic, antiarrhythmic, and anticonvulsant drugs. Catterall, WA; Ragsdale, DS; Scheuer, T, 1991)	0.56
") maternal serum concentrations of PHT, MPH, and ETH 1 hour after dosing on gestational day 18 were 16."	( Comparison of the behavioral teratogenic potential of phenytoin, mephenytoin, ethotoin, and hydantoin in rats. Acuff-Smith, KD; Minck, DR; Vorhees, CV, 1991)	0.53
"Routine clinical pharmacokinetic data collected from patients receiving phenytoin have been analysed to propose a new and simple equation to aid the dosage adjustment of this drug."	( One-point feedback control method for phenytoin dosage adjustment. Aoyama, T; Higuchi, S; Yukawa, E, 1991)	0.78
" After a 4-week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations."	( Pharmacokinetic and dose tolerability study of ADD 94057 in comedicated patients with partial seizures. Cereghino, JJ; Laxer, KD; Manning, LW; McCormick, C; Pledger, GW; Sahlroot, JT; Taylor, MR; Whitley, L, )	0.13
"Mice of the A/J and C57BL/6J (C57) strains were dosed with phenytoin (PHT) every 48 hr throughout pregnancy by gastric intubation to test the hypothesis that maternal plasma PHT concentration may be the significant factor in determining PHT reproductive and developmental toxicity."	( Phenytoin teratogenicity and midgestational pharmacokinetics in mice. Laborde, JB; Roberts, LG; Slikker, W, 1991)	1.97
"A simple and practical graphic method based on Bayesian feedback theory for predicting individual phenytoin dosage was evaluated."	( A Bayesian graphic method for predicting individual phenytoin dosage schedule. Cai, WM; Chen, G; Chu, XM, 1991)	0.75
" Attempts to achieve more consistent peroral phenytoin bioavailability from conventional solid dosage forms include changes of binder and crystal size, use of salt form, and inclusion of the drug in cyclodextrins."	( Bioavailability study of a freeze-dried sodium phenytoin-milk formulation. Ismailos, G; Macheras, P; Reppas, C, 1991)	0.8
" The dramatic response of our patients to cyclophosphamide, which is known to inhibit cell-mediated cytotoxicity by inhibiting both the recognition and lethal hit stages, together with the rapid regrowth of the epidermis within 4 days to a week in patients who received adequate dosage of the drug, supports the preceding concepts."	( Efficacy of cyclophosphamide in toxic epidermal necrolysis. Clinical and pathophysiologic aspects. Allen, SG; Heng, MC, 1991)	0.28
" The clearance of phenytoin and p-HPPH was determined by rate of dosing divided by the steady-state concentration."	( Stereoselective inhibition of diphenylhydantoin metabolism by p-hydroxyphenyl-phenylhydantoin enantiomers in rats. Hsieh, CY; Huang, JD, 1991)	0.62
" Plasma concentrations of paroxetine at steady state (8-147 ng/ml) were in the normal range for a 30-mg daily dosing regimen."	( No influence of the antidepressant paroxetine on carbamazepine, valproate and phenytoin. Andersen, BB; Dam, M; Kristensen, HB; Lund, J; Mengel, H; Mikkelsen, M; Pedersen, B; Vesterager, A, )	0.36
" Carbamazepine in moderate dosage adversely affected memory, but sodium valproate and phenytoin did not."	( Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. Berg, I; Butler, R; Forsythe, I; McGuire, R, 1991)	0.73
"The relationship between a dose of phenytoin and the resultant serum concentration is difficult to predict, and numerous dosing methods have been developed to quantify the dose required to achieve a specific concentration."	( An updated comparison of drug dosing methods. Part I: Phenytoin. Erdman, SM; Pryka, RD; Rodvold, KA, 1991)	0.81
" Only one subject tolerated discontinuation of CBZ; the other three had dosage reductions of 33, 54, and 63%."	( Discontinuation of phenytoin and carbamazepine in patients receiving felbamate. Graves, NM; Holmes, GB; Leppik, IE; Marienau, K; Remmel, RP; Wagner, ML, )	0.46
" Its pharmacokinetic features and optimal dosage show great individual variability, larger than that of other drugs and, in cases of combined drug regimens, interactions may more frequently be expected."	( Place of phenytoin in treatment of resistant epilepsy. Rajna, P; Veres, J; Vitray, J, 1991)	0.7
" Iatrogenic causes of intoxication were common and included increased daily dosage and intravenous loading in the emergency room for single seizures in patients with subtherapeutic serum phenytoin levels."	( Phenytoin intoxication. Devinsky, O; Motiwala, R; Murphy, JM, 1991)	1.91
" The mean felbamate dosage was 2,300 mg/d."	( Felbamate for partial seizures: results of a controlled clinical trial. Bertram, E; Cereghino, JJ; Dreifuss, FE; Drury, I; Graves, NM; Jacobs, MP; Leppik, IE; Pledger, GW; Santilli, N; Tsay, JY, 1991)	0.28
" In order to use these effectively, the critical care nurse must be aware of the indications and controversies surrounding their use, the patho-physiologic conditions that impact on the disposition, and appropriate dosing and monitoring of these agents in the critical care setting."	( Anticonvulsants: pharmacotherapeutic issues in the critically ill patient. Dupuis, RE; Miranda-Massari, J, 1991)	0.28
" Of 320 patients monitored, 190 patients whose seizures were uncontrolled were followed up before and after dosage adjustment was carried out."	( Need for 25 mg tablets of phenytoin. Dalvi, SS; Joshi, MV; Kshirsagar, NA; Shah, PU, 1991)	0.58
" Findings show that timing recommendations for dosing in relation to meals are not considered in these institutions when drug administration schedules are established."	( Drug administration in relation to meals in the institutional setting. Kinder, S; Lubischer, A; Strong, A; Wolff, H, 1991)	0.28
" Phenytoin (PHT) dosage had to be increased in 85% of pregnancies in which the drug was received, carbamazepine (CBZ) dosage in 70%, and phenobarbital (PB) or methylphenobarbital (MPB) dosage in 85%, in an attempt to prevent or correct a fall in plasma concentrations of the respective drugs as pregnancy progressed."	( Plasma antiepileptic drug concentrations during pregnancy. Eadie, MJ; Lander, CM, )	1.04
" Serum concentration monitoring with a reduction in phenytoin dosage is clinically warranted in patients receiving phenytoin and concomitant fluconazole therapy."	( Effect of fluconazole on the disposition of phenytoin. Blum, RA; Gardner, MJ; Harrison, NJ; Henry, EB; Hilligoss, DM; Schentag, JJ; Wilton, JH, 1991)	0.79
"Previous publications described computer-aided methodology for assessing the feasibility of designing prolonged release oral dosage forms containing linear-disposition drugs."	( Computer-aided dosage form design. III. Feasibility assessment for an oral prolonged-release phenytoin product. Irvin, JR; Notari, RE, 1991)	0.5
"Stochastic simulations were used to examine the sensitivity of mean phenytoin steady state concentrations (Css) to changes in the effective dosing rate produced by differences in average product content or bioavailability."	( Sensitivity analysis of the effect of bioavailability or dosage form content on mean steady state phenytoin concentration. Allerheiligen, SR; Browne, TR; Koup, JR; Ludden, TM, 1991)	0.73
" In order to define the minimal dosage of fentanyl required, the MD was titrated according to increases or decreases in the heart rate and/or mean arterial pressure exceeding 15 per cent of baseline ward values."	( Anticonvulsant therapy increases fentanyl requirements during anaesthesia for craniotomy. Modica, PA; Spitznagel, EL; Tempelhoff, R, 1990)	0.28
" Blood and urine samples in the studies were collected during a dosing interval at steady state."	( Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid. Acheampong, A; Anderson, GD; Baillie, TA; Friel, PN; Guyot, M; Levy, RH; Loiseau, P; Rettenmeier, AW; Tor, J; Wilensky, AJ, 1990)	0.57
" Individual dosage adjustment is preferably based on clinical judgment rather than on published therapeutic ranges."	( [High-dose monotherapy in intractable epilepsy]. Peng, SM; Wu, JZ, 1990)	0.28
" It is suggested that in those cases where tubing is placed into the duodenum, inadequate gastrointestinal residence time for dissolution of phenytoin solid and suspension dosage forms coupled with irreversible drug loss from solution to NG tubing will result in decreased phenytoin absorption and subsequently lower drug plasma levels."	( Phenytoin interaction with enteral feedings administered through nasogastric tubes. Fleisher, D; Kou, JH; Sheth, N, )	1.78
" This article reviews the indications, dosing regimens, and potential side effects of the drugs used for the treatment of trigeminal and glossopharyngeal neuralgia, posttherapeutic neuralgia, temporal arteritis, and migraine based on the clinical pharmacology of these drugs, so that the most appropriate treatment for each patient can be chosen on a sound, rational basis."	( Clinical pharmacology of drugs used to treat head and face pain. Fromm, GH, 1990)	0.28
" There were 756 steady-state PHT concentrations and associated dosage rates (mg/d) from 334 outpatients."	( Population pharmacokinetics of phenytoin from routine clinical data in Japan: an update. Aoyama, T; Higuchi, S; Yukawa, E, 1990)	0.57
" The dosage of QYS was 100 mg/kg/QOD and the period of administration was one month."	( The investigation of antiepileptic action of qingyangshen (QYS)--influences of QYS on the development of rat brain and memory behavior. Kuang, P; Lang, S; Liu, J; Zhang, X; Zhu, K, 1990)	0.28
" Eighty-four patients had been established on treatment with a single anticonvulsant drug (35 carbamazepine (CBZ), 30 sodium valproate (VPA), 19 phenytoin (PHT)) at unaltered dosage for the previous 3 months."	( Cognitive function in adult epileptic patients established on anticonvulsant monotherapy. Brodie, MJ; Butler, E; Gillham, RA; Larkin, JG; Wiedmann, KD; Williams, N, 1990)	0.48
" These findings should therefore be considered when defining dosage regimens or interpreting serum drug concentrations."	( Analysis of the factors influencing anti-epileptic drug concentrations--valproic acid. Aoyama, T; Higuchi, S; Hirata, K; Ieiri, I; Yamada, H, 1990)	0.28
"Five methods to predict phenytoin dosage have been compared in nine continuous care elderly patients."	( Phenytoin dosage individualization--five methods compared in the elderly. Farquhar, DL; Hudson, SA; Smith, RG; Thompson, D, 1990)	2.03
") maternal serum concentrations of total phenytoin 1 hr after dosing on E18 were 15."	( Dose-response effects of prenatal phenytoin exposure in rats: effects on early locomotion, maze learning, and memory as a function of phenytoin-induced circling behavior. Acuff, KD; Minck, DR; Vorhees, CV; Weisenburger, WP, )	0.68
" Serum blood levels should be checked, and dosage adjusted before the addition of antidepressant medication."	( Dilantin toxicity and vegetative depression: a report of two cases. Garrison, SJ; Henson, HK, 1990)	0.28
" All dosage reductions should be guided by clinical and therapeutic drug monitoring."	( Steady-state interaction between amiodarone and phenytoin in normal subjects. Bliss, M; Erstad, BL; Gear, K; Hoyer, GL; Marcus, FI; Nolan, PE, 1990)	0.53
"Phenytoin (PHT) is a commonly used drug in children and adults, but it is often difficult to adjust the dosage to attain therapeutic drug concentrations due to the nonlinear nature of PHT metabolism."	( Phenytoin dosage adjustment method using population clearance. Aoyama, T; Higuchi, S; Yukawa, E, 1990)	3.16
"Pigeons were trained in a cumulative dosing procedure to emit one response in the presence of 15 mg/kg phenytoin and another response in the absence of phenytoin."	( Discriminative stimulus properties of phenytoin in the pigeon: determination via a cumulative dosing procedure. Clark, R; Poling, A; Schlinger, H, 1990)	0.77
" The repeated dosing of allopurinol at higher doses (20 and 50 mg/kg) significantly retarded the elimination of DPH from the circulation and dramatically decreased the urinary excretion of p-hydroxyphenytoin (HPPH), a major metabolite of DPH."	( Drug interaction between phenytoin and allopurinol. Ito, Y; Iwaki, M; Ogiso, T; Tsunekawa, K, 1990)	0.77
" Two separate dose-response tests were also conducted with DPH and HPPH with a MAS modulated by various mixed functional oxidase inhibitors [carbon monoxide (CO) (broad spectrum cytochrome P450), cimetidine (mainly cytochrome P450), and ellipticine (cytochrome P448)] and an epoxide hydrolase inhibitor (cyclohexene oxide)."	( Use of Frog Embryo Teratogenesis Assay-Xenopus and an exogenous metabolic activation system to evaluate the developmental toxicity of diphenylhydantoin. Bantle, JA; Fort, DJ, 1990)	0.28
" Therefore, 300-mg extended PHT sodium capsules can be safely and effectively interchanged with three 100-mg extended PHT sodium capsules in patients requiring a once-daily 300-mg PHT sodium dosing regimen."	( Pharmacokinetic profile of a 300-mg extended phenytoin sodium capsule (Dilantin) formulation. Buchanan, RA; Kinkel, AW; Randinitis, EJ, )	0.39
" She had been treated for hypothyroidism as well as migraine with abnormal electroencephalogram since age 47, and was given a daily dosage of 70 mg phenytoin, 80 mg phenobal, and 125 mg dried thyroid."	( [A case of involuntary movements probably produced by low doses of phenytoin intoxication]. Itou, H; Morimatsu, M; Noda, S; Umezaki, H; Yamamoto, K, 1990)	0.71
" The capability predicting individual phenytoin dosage was assessed by the retrospective analysis of data of 44 patients and the prospective analysis of 15 patients."	( [Population kinetic program for Michaelis-Menten elimination]. Lü, M; Song, JF; Zhou, HW, 1990)	0.55
" The technique is simple and rapid: 4 anticonvulsants are simultaneously extracted and dosed, valproic acid, only has to be dosed lonely."	( [Plasma determination of 7 common drugs by high performance liquid chromatography]. Baty, C; Jambou, J; Leducq, B; Richard, L, 1989)	0.28
" When the drug was repeatedly coadministered with DPH or CBZ, the initial VPA elimination from plasma up to 1 h after dosing was less than with VPA alone, while PB significantly enhanced the disappearance of VPA."	( Effects of anticonvulsants on plasma levels and entero-hepatic circulation of valproic acid and on hepatic drug metabolizing enzyme activities in rats. Horibe, Y; Ito, Y; Iwaki, M; Ogiso, T; Yoneda, I, 1989)	0.28
" The dose-response curve of PHT was described as a first-order reaction with Kd = 37 microM; 100 microM CBZ was equally as effective 100 microM PHT."	( Phenytoin and carbamazepine: potential- and frequency-dependent block of Na currents in mammalian myelinated nerve fibers. Grigat, G; Schwarz, JR, )	1.57
" However, the effect of carbamazepine (100 microM) on the respective dose-response curves suggests that the mechanism of inhibition of the carbachol response differs from the inhibition of the histamine and veratrin responses."	( Inhibition of agonist-stimulated inositol lipid metabolism by the anticonvulsant carbamazepine in rat hippocampus. Logan, SD; McDermott, EE, 1989)	0.28
" In this prospective, descriptive study four dosage regimens were investigated in 104 patients."	( Clinical experience with phenytoin prophylaxis in severe preeclampsia. Lange, IR; Naugler, MA; Ryan, G, 1989)	0.58
" These results support the increased use of dosing aids for PHT that may help clinicians more accurately choose PHT doses and estimate time to steady state."	( Dosing accuracy of antiepileptic drug regimens as determined by serum concentrations in outpatient epilepsy clinic patients. Privitera, MD, 1989)	0.28
" A dose-response study was followed by a detailed teratological study using a single dose of 3 mg."	( Teratogenic effects of phenytoin on chick embryos. Shah, GL; Singh, M, 1989)	0.59
"We investigated the influence of the population pharmacokinetic parameters on the performance of the Bayesian feedback method in predicting the phenytoin (PHT) dosage needed to achieve a desired PHT serum concentration."	( Clinical evaluation of population pharmacokinetic parameters in phenytoin dosage adjustment. Aoyama, T; Higuchi, S; Yukawa, E, 1989)	0.72
" This method was found to be sufficiently applicable to the analyses of the serum concentrations of phenytoin at non-steady state as well as at steady state and the dosage adjustment by simulation."	( Development of the convenient and direct numerical analytical method of the pharmacokinetics of phenytoin by an ordinary and/or the Bayesian weighted least-squares method using the program MULTI2(BAYES). Fujita, T; Koshiro, A, 1989)	0.71
" All patients required a PHT dosage decrease of 10-30% during active FBM treatment to maintain stable concentrations."	( Effect of felbamate on phenytoin and carbamazepine serum concentrations. Fuerst, RH; Graves, NM; Holmes, GB; Leppik, IE, )	0.44
"A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin."	( Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy. Albani, F; Baruzzi, A; Bianchi, A; Messori, A; Muscas, GC; Riva, R; Valenza, T; Zaccara, G; Zagnoni, P; Zolo, P, )	0.58
"In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments."	( [Dosage adjustment of drugs during continuous hemofiltration. Results and practical consequences of a prospective clinical study]. Dehne, M; el Abed, K; Hofmann, W; Kroh, U; Lennartz, H, 1989)	0.28
" Steep dose-response curves are obtained by relating the observed inhibition to the free biotin concentration."	( Pyruvate carboxylase as a model for oligosubstituted enzyme-ligand conjugates in homogeneous enzyme immunoassays. Bachas, LG; Daunert, S; Payne, BR, 1989)	0.28
" Serious consequences can be avoided by expecting changes in phenytoin dosage requirements after the administration of chemotherapy, monitoring serum levels frequently, and making appropriate adjustments in phenytoin dosages."	( Decreased phenytoin levels in patients receiving chemotherapy. Gilbert, MR; Grossman, SA; Sheidler, VR, 1989)	0.92
" Dose-response curves for the behavioral and antiseizure effects of phenobarbital were similar."	( Effects of phenytoin and phenobarbital on schedule-controlled responding and seizure activity in the amygdala-kindled rat. Jakubow, J; Poling, A; Renfrey, G; Schlinger, H, 1989)	0.67
"Phenytoin dosing in paediatric patients is complicated both by alterations in patient requirements due to growth and maturation changes and by the capacity-limited characteristics of phenytoin metabolism."	( Phenytoin dosage predictions in paediatric patients. Latimer, PT; Littlefield, LC; Mackey, RW; Yuen, GJ, 1989)	3.16
"A computer program for phenytoin (PHT) dosing was developed containing seven different menus: two for drug-naive patients, one using an empirical equation, the other using means for Vmax and Km; two for patients in whom either one or two dose rates and steady-state concentrations are available; two for patients with hypoalbuminemia, and uremia, respectively; and one menu that optimizes Vmax and Km from available steady-state concentrations."	( Evaluation of a phenytoin dosage regimen design and adjustment computer program. Alcorn, GJ; Fogelson, MH; Johnson, RD; Rao, S; Ritschel, WA, 1989)	0.93
" Our study demonstrates that current IV dosing of phenobarbital 20 mg/kg given intraosseously obtains and maintains therapeutic serum levels."	( Comparison of intraosseous and intravenous routes of anticonvulsant administration in a porcine model. Jaimovich, DG; Peters, GR; Ringer, TV; Shabino, CL, 1989)	0.28
" Steady-state apparent plasma clearances of phenytoin (dose/steady-state concentration) correlated closely with simultaneous plasma clearances of the intravenous stable-isotope drug (measured as dose/AUC) suggesting that the patients were complaint with therapy when their phenytoin dosage requirement increased during the pregnancy, and that the oral drug was fully bioavailable."	( The effect of pregnancy in humans on the pharmacokinetics of stable isotope labelled phenytoin. Dickinson, RG; Eadie, MJ; Hooper, WD; Lander, CM; Wood, B, 1989)	0.76
"Wagner proposed a new and simple method to predict dosage of drugs obeying simple Michaelis-Menten elimination kinetics."	( Clinical utility of a new and simple technique for individualizing phenytoin dosage. Aoyama, T; Higuchi, S; Yukawa, E, 1989)	0.51
" The 90 per cent confidence interval expressed as a percentage of the reference mean for Tmax, Cmax, and AUC 0-infinity showed model dependent changes from single to multiple dosing in response to the level of data error and changes in absorption."	( Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics. Jackson, AJ, )	0.13
" The low dosage reduced total AD accrued during each kindling stage but failed to alter kindling rate."	( The NMDA-receptor antagonist, MK-801, suppresses limbic kindling and kindled seizures. Gilbert, ME, 1988)	0.27
" High drug dosage contributed most to abnormal serum biochemical test results, and combining phenytoin with primidone was responsible for more severe electron microscopic lesions of the liver of surviving dogs and for the death of 3 dogs."	( Effects of long-term primidone and phenytoin administration on canine hepatic function and morphology. Baldwin, BH; Bunch, SE; Castleman, WL; Hornbuckle, WE; Tennant, BC, 1985)	0.77
" Serious adverse reactions necessitate a change in antiarrhythmic therapy, as opposed to lowering drug dosage to an ineffective level."	( Antiarrhythmic drug therapy. Recent advances and current status. Somberg, J, 1985)	0.27
"25 mg/kg) during anesthesia with O2/N2O/fentanyl, to generate dose-response curves for the relaxants."	( The effect of phenytoin on the magnitude and duration of neuromuscular block following atracurium or vecuronium. Diaz, J; Matteo, RS; Ornstein, E; Schwartz, AE; Silverberg, PA; Young, WL, 1987)	0.63
" Frequency and extent of increased activity of gamma-GT were highly related to daily dosage in both preparations."	( The influence of long-term anticonvulsant therapy with diphenylhydantoin and carbamazepine on serum gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. Aldenhövel, HG, 1988)	0.27
" Frequency and extent of increased activity of gamma-GT were highly related to daily dosage in both preparations."	( [Altered gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase serum activities in long-term anticonvulsive therapy--comparison of diphenylhydantoin and carbamazepine]. Aldenhövel, HG, 1988)	0.27
" There were 505 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 220 out-patients."	( Population pharmacokinetics of phenytoin from routine clinical data in Japan. Aoyama, T; Higuchi, S; Yukawa, E, 1989)	0.85
" In the N3 nitrogen-substituted series one compound, 5,5-diphenyl-N3-n-butyl-2-thiohydantoin, DPBTH (7), showed promise during initial screening, but when analyzed in a dose-response study, its activity was considerably less than that of the parent compound DPTH."	( 5,5-Diaryl-2-thiohydantoins and 5,5-diaryl-N3-substituted-2-thiohydantoins as potential hypolipidemic agents. Tompkins, JE, 1986)	0.27
"Safety and efficacy studies of new antiepileptic drugs require strict adherence to prescribed dosage regimens."	( Compliant populations: variability in serum concentrations. Graves, NM; Holmes, GB; Leppik, IE, 1988)	0.27
" In the case of diazepam, clonazepam, ethosuximide or trimethadione, the TE/TF ratio was decreased dose-dependently, but the slope of the dose-response regression line was less steep than that obtained by the administration of PB, PNT, CBZ, VPA or primidone."	( [The correlation between concentrations of anticonvulsive drugs in the brain and various parameters of maximal electroshock seizures in mice]. Kishita, C, 1986)	0.27
" The two cortical sites were distinguished by significantly different dose-response curve slopes for the suppression of afterdischarge duration by PHT, CBZ and VPA, which suggests more than one mechanism of action for these drugs."	( Differential antiepileptic sensitivity between cortical sites in the rat. Iragui, VJ; Kalichman, MW; Moss, KA, )	0.13
" The higher the administered dosage is, the better the degree of recovery of EEG was seen."	( [Protective effect of phenytoin and its enhanced action by combined administration of mannitol and vitamin E in cerebral ischemia]. Abiko, H; Mizoi, K; Oba, M; Suzuki, J; Yoshimoto, T, 1986)	0.59
" The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment."	( Carbamazepine efficacy in adults with partial and generalized tonic-clonic seizures. Rangel, R; Wilder, BJ, 1987)	0.27
" We founded a good relationship between PRI dosage and PB plasma levels."	( [Usefulness of the evaluation of plasma levels of primidone and phenobarbital]. Franzoni, E; Govoni, M; Mambelli, M; Masoni, P, )	0.13
"PEDA, an integrated program in BASIC for implementation on microcomputers, has been developed for use in clinical practice to assist dosage adjustment for individual patients."	( PEDA: a microcomputer program for parameter estimation and dosage adjustment in clinical practice. Aoyama, T; Higuchi, S; Horioka, M, 1987)	0.27
" In response to the effects of enzyme induction, valproate dosage may need to be doubled to maintain therapeutic serum levels."	( Pharmacologic interactions between valproate and other drugs. Bourgeois, BF, 1988)	0.27
" In each patient, the average unbound fraction for a dosing interval increased with increase in sodium valproate dose."	( Changes in clearance of sodium valproate with changes in dose. Bury, RW; Fullinfaw, RO; Kilpatrick, CJ; Moulds, RF, 1987)	0.27
" In control animals, maternal plasma corticosterone levels were elevated soon after dosing but gradually declined, except for an apparent circadian rhythm effect seen in samples obtained in the afternoon."	( Alterations in maternal plasma corticosterone levels following treatment with phenytoin. Grafton, TF; Hansen, DK; Holson, RR; Sullivan, PA, 1988)	0.5
"This preliminary clinical study describes the pharmacokinetic characteristics of flunarizine (FLN) following single and multiple dosing in epileptic patients receiving comedication."	( Pharmacokinetic profile of flunarizine after single and multiple dosing in epileptic patients receiving comedication. Barber, K; Cereghino, JJ; Di Giorgio, C; Kapetanovic, IM; Kupferberg, HJ; Lau, M; Norton, L; Torchin, CD; Treiman, DM; Whitley, L, )	0.13
" Because it demonstrates saturable, Michaelis-Menten pharmacokinetics, dosing of phenytoin within the therapeutic range can be very challenging, especially so in obese patients."	( Phenytoin dosing in obese patients: two case reports. de Oca, GM; Gums, JG; Robinson, JD, 1988)	1.94
" Therefore many techniques have been advocated to aid dosage adjustments based on a single-point PHT concentration determined at steady-state (ss)."	( Comparison of single-point phenytoin dosage prediction techniques. Aoyama, T; Higuchi, S; Ohtsubo, K; Yukawa, E, 1988)	0.57
"Phenytoin (PHT) dosage adjustment in a clinical situation is difficult because of the nonlinear metabolism of the drug."	( Evaluation of single-point phenytoin dosage prediction methods in pediatric patients. Aoyama, T; Higuchi, S; Yukawa, E, 1988)	2.01
" Among these are various disease states, obesity, fluid imbalances, the drug dosage form used, and concurrent drug use."	( Use of serum drug concentrations in surgical patients. Connors, JE; DiPiro, JT; Sisley, JF, 1988)	0.27
" Thus, frequent phenytoin serum concentration determinations or a change in phenytoin dosing rate are probably not necessary after adding phenobarbital."	( Phenobarbital does not alter phenytoin steady-state serum concentration or pharmacokinetics. Browne, TR; Evans, BA; Evans, J; Greenblatt, DJ; Mikati, MA; Szabo, GK, 1988)	0.91
" By means of Monte Carlo simulations an optimal dosing scheme for phenytoin loading has been calculated."	( Intravenous phenytoin loading in patients after neurosurgery and in status epilepticus. A population pharmacokinetic study. Aarons, L; Gratzl, O; Landolt, H; Maitre, P; Uematsu, T; Vozeh, S, 1988)	0.89
" PHT dosage had been increased 4 months earlier."	( [Recurrent acute dyskinesia as the sole manifestation of phenytoin poisoning]. Koskas, P; Mahieux, F; Marteau, R; Roullet, E, 1987)	0.52
" Addition of this same antibody to teratogenic sera from dosed monkeys improved the development of cultured embryos and provided additional support for this complex as the proximal teratogen."	( Identification of a teratogenic drug-protein complex in sera of phenytoin-treated monkeys. Clapper, ML; Klein, NW, )	0.37
" This method involves prediction of the oral maintenance dosage from data obtained following the administration of an intravenous loading dose."	( Evaluation of a proposed method for phenytoin maintenance dose prediction following an intravenous loading dose. Crowley, JJ; Cusack, BJ; Koup, JR; Ludden, TM; Vestal, RE, 1987)	0.55
"6 mumol/l respectively, determined by using total serum concentration, could be to estimate phenytoin dosage requirements in a hospital population."	( Population pharmacokinetics of phenytoin in South African black patients. Klein, C; Miller, R; Rheeders, M; Suchet, I, 1987)	0.78
" Phenytoin dosage must be individualized to achieve concentrations of 10-20 micrograms/ml."	( Interindividual variation in the extent and rate of phenytoin accumulation. Chang, T; Levine, M; Orr, J, 1987)	1.43
" Vmax and Km were graphically estimated from plasma concentrations at varying phenytoin dosage regimens in 36 of the patients."	( The debrisoquin hydroxylation phenotype does not predict the metabolism of phenytoin. Alván, G; Garle, M; Lind, M; Maguire, JH; McClanahan, JS; Nilson, SO; Sjöqvist, F; Steiner, E; Tomson, T, 1987)	0.73
" This was followed by an intravenous loading dose of phenytoin sodium and oral maintenance dosing for 2 weeks, after which the intravenous theophylline study was repeated."	( Cigarette smoking and theophylline metabolism: effects of phenytoin. Crowley, JJ; Cusack, BJ; Jue, SG; Koup, JR; Vestal, RE, 1987)	0.77
" Maze errors also showed a clear dose-response relationship in the new maze, while no such distinctions were seen in the Biel maze."	( Maze learning in rats: a comparison of performance in two water mazes in progeny prenatally exposed to different doses of phenytoin. Vorhees, CV, )	0.34
" In 48% of the patients the drug dosage had to be increased to combat the increased seizure frequency."	( Serum phenytoin during pregnancy, labor and puerperium. Bardy, AH; Hiilesmaa, VK; Teramo, KA, 1987)	0.75
" Cortisol hydroxylation was increased in the group of epileptics with large inter-individual variations notwithstanding a similar dosage of inducers."	( Urinary 6-beta-OH-cortisol and paracetamol metabolites as a probe for assessing oxidation and conjugation of chemicals in humans. Dolara, P; Lodovici, M; Muscas, GC; Salvadori, M; Zaccara, G, 1987)	0.27
" Additional serum concentrations and dosing data were collected as they became available, but no effort was made to control the number or timing of serum concentration determinations."	( Evaluation of a Bayesian regression-analysis computer program using non-steady-state phenytoin concentrations. Clementi, WA; Godley, PJ; Godley, SE; Ludden, TM; Ramsey, RR, 1987)	0.5
"The predictive abilities of the following four single-point phenytoin dosage adjustment methods were compared using computer-simulated data: the Bayesian feedback method of Vozeh et al."	( Comparison of four single-point phenytoin dosage prediction techniques using computer-simulated pharmacokinetic values. Jameson, JP; Toscano, JP, 1986)	0.8
" Phenytoin is available from a variety of manufacturers in a variety of dosage forms."	( Review of alterations in oral phenytoin bioavailability associated with formulation, antacids, and food. Cacek, AT, 1986)	1.47
" These findings suggest that the dosage of zonisamide in epileptic patients might need to be varied depending on the comedication."	( Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy. Buchanan, RA; Friel, PN; Levy, RH; McLean, JR; Ojemann, LM; Shastri, RA; Wilensky, AJ, 1986)	0.49
" The most common of these causes include malpractice of the dosage build-up in the absence of the clinical effect, polytherapy--not infrequently with drugs of the same chemical group, and insufficient attention to the potentiating drug interaction."	( [Phenomenon of "paradoxical poisoning" during antiepileptic therapy]. Geladze, TSh, 1986)	0.27
" For two different dosage regimens that each subject received, the last available predose concentration on the sixth day of the regimen was predicted using observed predose concentrations on both the morning of the third day and on each of the first three days of phenytoin administration."	( Evaluation of a Bayesian regression-analysis computer program for predicting phenytoin concentration. Beal, SL; Godley, PJ; Ludden, TM; Peck, CC, 1986)	0.68
" The results of these studies indicate that the low blood concentrations of phenytoin resulting from the relatively high daily dosage of phenytoin in infants, when compared to adults, cannot be explained on the basis of poor oral absorption of phenytoin."	( Phenytoin metabolism in infants following intravenous and oral administration. Fischer, LJ; Leff, RD; Roberts, RJ, 1986)	1.94
" Dose-response curves for the convulsive effect of pentylenetetrazol obtained at the peak of the withdrawal signs shifted greatly to the left in alcohol withdrawn animals but less in barbital withdrawn animals."	( Differentiation of alcohol and barbital physical dependence. Kaneda, H; Kaneto, H; Kawatani, S, 1986)	0.27
" Data were excluded for patients who required dosage adjustments because of toxicity or seizures."	( Effect of influenza vaccine on serum anticonvulsant concentrations. Fidone, GS; Jann, MW, 1986)	0.27
" A train of focal and generalized seizure discharges (SDs) induced by electrical stimulation was compared before and after dosing with PHT."	( Antiepileptic effects under steady state of phenytoin serum levels produced in acute experiments. Hirose, S; Jibiki, I; Kubota, T; Yamaguchi, N, )	0.39
"The saturable elimination kinetics of phenytoin (PHT) makes accurate dosing difficult."	( Phenytoin clearances in a compliant population: description and application. Graves, NM; Leppik, IE; Taylor, JW; Termond, E, 1986)	1.98
"For many drugs estimation of a safe and effective dosage regimen is difficult."	( Computerized drug therapy: application of the hand-held microcomputer to dosage regimen design. Brouwer, KR; Cook, J; Gwilt, PR; Steinke, M, 1985)	0.27
" The provision of appropriate support services (assay results and dosage advice) to specialist epilepsy clinics allows improvement in the management of epilepsy."	( Availability of drug assay results and dosage advice improves antiepileptic care in a specialist neurology outpatient clinic. Gilligan, BS; Harrison, PM; Heinzow, U; Horne, M; Ioannides-Demos, LL; McLean, AJ; Tong, N; Wodak, J, 1985)	0.27
"The literature reviewed herein clearly demonstrates the poor correlation between drug dosing and the ability to achieve a specific serum drug concentration and between drug dosing and clinical response, especially for drugs with a narrow therapeutic index."	( Comparison of drug dosing methods. Brater, DC; Burton, ME; Vasko, MR, )	0.13
"To evaluate empiric dosing guidelines for aminophylline and phenytoin in the management of acute exacerbations of obstructive lung disease and seizure disorders, we utilized an emergency department (ED)-based EMIT system to measure stat plasma theophylline and phenytoin levels in patients intended to receive these drugs."	( Effect of empiric dosing on blood levels of theophylline and phenytoin. Bederka, J; Curtis, RA; Hutchinson, RA; Troyer, WG, 1985)	0.75
" If necessary the dosage has to be reduced or medication stopped."	( [Acute liver necrosis caused by valproate]. Hackenberg, K; Rengeling, M; Rühl, G; Zäh, W, 1985)	0.27
" Acute intraperitoneal administration of the other drugs revealed VPA to be an effective anticonvulsant agent, whereas ethosuximide and diazepam were ineffective at dosage levels that are normally effective in mice as determined by classical testing methods such as electroshock and chemoshock."	( Seizure control following administration of anticonvulsant drugs in the quaking mouse. Abbott, LC; Bennett, GD; Finnell, RH; Taylor, SM, 1985)	0.27
" In addition, the pharmacology of the drugs must be of such an order of complexity that there is not a simple relationship between dosage and serum levels."	( Serum theophylline and phenytoin levels: can we afford to do them? Can we afford not to? Kuhn, G, 1986)	0.58
"Fifty-nine patients with chronic generalized tonic-clonic or partial seizures refractory to the maximally tolerated daily dosage of single-drug therapy with carbamazepine, phenytoin, phenobarbital, or primidone subsequently received single-drug therapy with another one of these primary anticonvulsant drugs."	( Alternative single anticonvulsant drug therapy for refractory epilepsy. Richter, K; Schmidt, D, 1986)	0.46
"In an attempt to evaluate the accuracy of phenytoin (PHT) pharmacokinetic dosage adjustments in a private practice setting, three single dose-concentration pair methods and three multiple point PHT pharmacokinetic dosing methods were studied."	( A comparison of phenytoin dosing methods in private practice seizure patients. Mayer, PR; Robinson, FC; Welty, TE, )	0.74
" Phenytoin apparent pharmacokinetic and biotransformation values undergo a typical series of changes after beginning monotherapy at typical dosing rates, because PHT's dose-dependent pharmacokinetics result in differing apparent values as the serum concentration rises to steady state."	( Studies with stable isotopes I: Changes in phenytoin pharmacokinetics and biotransformation during monotherapy. Browne, TR; Evans, BA; Evans, JE; Greenblatt, DJ; Schumacher, GE; Szabo, GK, )	1.3
" When data before metronidazole dosing were compared with those after metronidazole dosing, there were no changes in total plasma clearance of diazepam (0."	( Interaction between metronidazole and drugs eliminated by oxidative metabolism. Gugler, R; Jensen, JC, 1985)	0.27
"Until now, no evaluation of phenytoin dosing methods has been undertaken in a large group of patients, to our knowledge."	( Comparison of eight phenytoin dosing methods in institutionalized patients. Flint, N; Lopez, LM; Robinson, JD; Salem, RB; Williams, C, 1985)	0.89
" Among Chinese epileptic patients, the saturation of phenytoin metabolism occurs at the dosage of 4 mg/kg/day."	( Steady-state serum levels of anticonvulsant drugs in Chinese epileptic patients living in Taiwan. Lai, ML, 1985)	0.52
" On the other hand, pretreatment with phenytoin increased the responsiveness of animals dosed with chlordecone or lindane, suggesting that these agents differ in their mechanism of action from p,p'-DDT and permethrin."	( Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin. Hong, JS; Mactutus, CF; Tilson, HA, 1985)	0.82
" None of the dosing regimens caused toxicological manifestations other than hepatomegaly."	( Alteration of bone marrow cell cycle kinetics by diphenylhydantoin: relationship to folate utilization and immune function. Boorman, GA; Hong, L; Luster, MI; Pung, O; Tucker, AN, 1985)	0.27
" A time course of DPH-d10 concentrations was followed simultaneously with DPH-d0 during dosing intervals by GC-MS, with DPH-d5 as an internal standard."	( Stable-isotope methodology for the bioavailability study of phenytoin during multiple-dosing regimens. Baba, S; Kasuya, Y; Mamada, K; Matsukura, M, 1985)	0.51
" After a minimum of 10 half-lives of maintenance dosing on a fixed regimen, the accumulation of propylene glycol differed significantly among individuals because of variability in apparent clearance."	( Pharmacokinetics of propylene glycol in humans during multiple dosing regimens. Elmquist, WF; Sawchuk, RJ; Yu, DK, 1985)	0.27
" The dosage was about 80 mg/kg."	( Alterations in tissue trace element and ascorbic acid metabolism in phenytoin-fed rats and mice. Dubick, MA; Keen, CL, 1985)	0.5
"-1 the lower end of the teratogenic dose-response curve was determined for each drug."	( Fetal anticonvulsant syndrome in rats: effects on postnatal behavior and brain amino acid content. Vorhees, CV, )	0.13
"Antipyrine total clearance and the formation clearance of its major metabolites were studied in normal, healthy male volunteers before and after multiple dosing for approximately three weeks with phenytoin (six subjects) and carbamazepine (six subjects)."	( Antipyrine metabolite kinetics in healthy human volunteers during multiple dosing of phenytoin and carbamazepine. Hopkins, K; Houston, JB; Morselli, PL; Rowland, M; Shaw, PN; Thiercelin, JF, 1985)	0.68
" No detectable change in T(4) deiodination rate was observed with these agents in the dosage ranges employed in this study."	( A new method for the measurement of acute alterations in thyroxine deiodination rate in man. Nicoloff, JT, 1970)	0.25
"Blood phenytoin (diphenylhydantoin) concentrations were measured after each dosage change in 12 epileptic patients who were given increasing oral doses of phenytoin."	( Effect of dosage increments on blood phenytoin concentrations. Bochner, F; Eadie, MJ; Hooper, WD; Tyrer, JH, 1972)	1
"The results indicate that failure to follow dosage instructions is a factor of major importance among epileptic patients whose response to treatment is inadequate or erratic."	( Supervision of epileptic patients taking phenytoin. Dunne, JF; Gibberd, FB; Handley, AJ; Hazleman, BL, 1970)	0.51
" Hypocalcaemia was related to high dosage of anticonvulsant drugs, to multiple drug therapy, and to the use of individual anticonvulsant drugs in the following order, with decreasing order of importance: pheneturide, primidone, phenytoin, phenobarbitone."	( Disturbance of calcium metabolism by anticonvulsant drugs. Richens, A; Rowe, DJ, 1970)	0.43
" Reduction of phenytoin dosage relieved the intoxication in all patients."	( Outbreak of anticonvulsant intoxication in an Australian city. Eadie, MJ; Hooper, WD; Sutherland, JM; Tyrer, JH, 1970)	0.61
" We found a noticeable relationship between conduction velocity slowing and daily dosage for CBZ only."	( Anticonvulsant therapy and its possible consequences on peripheral nervous system: a neurographic study. Faedda, MT; Geraldini, C; Sideri, G, 1984)	0.27
" Therefore, general dosage recommendations are useless and even dangerous, unless the preparations used are extensively specified."	( [Bio-availability of phenytoin free-acid serum level determinations whilst using a lactose-based tablet-preparation (author's transl)]. Fritsch, G; Füger, G; Haidvogl, M; Urban, C, 1980)	0.58
" An alteration in the dosage schedule is usually only necessary for drugs with a small therapeutic ratio."	( Clinical implications of enzyme induction and enzyme inhibition. Breckenridge, AM; Park, BK, )	0.13
"Patient compliance can be improved by reducing the complexity of drug dosage and by better labeling, packaging and informational exchange."	( Once-a-day drug regimen for psychiatric patients. Hasan, MK; Mooney, RP, 1981)	0.26
" Special consideration, however, must be given with regard to drug selection and dosage in order to avoid adverse effects on the mother and fetus."	( Antiarrhythmic drug therapy during pregnancy. Elkayam, U; Frishman, W; Rotmensch, HH, 1983)	0.27
" Administration of nitrazepam with other drugs, except aminopyrine, or of estazolam together with haloperidol exhibited an anticonvulsive pattern different from the case of dosing with either drug alone."	( [Pharmacology of a 1H-1, 2, 4-triazolyl benzophenone derivative (450191-S), a new sleep-inducer (III). Behavioral study on interactions of 450191-S and other drugs in mice]. Horiuchi, M; Ibii, N; Yamamoto, K, 1984)	0.27
" During steady-state conditions, however, this higher rate of absorption was associated with considerable fluctuations in plamsa concentration during the dosage interval."	( A comparison between microcrystalline and conventional phenytoin preparations: relative bioavailability and steady-state plasma concentrations. Boréus, LO; Ehrnebo, M; Nergårdh, A; Theorell, K, 1980)	0.51
" The controls were comprised of naive rats (G-VI) and naive rats dosed in the same manner as the dependent rats."	( Participant of serotonin turnover rate in the brain on barbital withdrawal convulsion. Hiramori, T; Nakao, K; Tagashira, E; Urano, T; Yanaura, S, 1982)	0.26
" In the first experiment, the lower end of the malformation dose-response curves for diphenylhydantoin (DPH), trimethadione (TMD) and phenobarbital (PB) were established."	( Fetal anticonvulsant syndrome in rats: dose- and period-response relationships of prenatal diphenylhydantoin, trimethadione and phenobarbital exposure on the structural and functional development of the offspring. Vorhees, CV, 1983)	0.27
" Her plasma phenytoin level at the time had dropped to 2 microgram/ml despite a recent dosage increase."	( Impaired phenytoin bioavailability secondary to cisplatinum, vinblastine, and bleomycin. Caldwell, KC; Lewis, FB; Lobell, M; Perri, R; Sawchuk, RA; Sylvester, RK, 1984)	1.06
" accommodation was enhanced) at the anesthetic dosage level."	( A comparison of the effects of pentobarbital and diphenylhydantoin on the GABA sensitivity and excitability of adult sensory ganglion cells. Connors, BW, 1981)	0.26
" Step clamp data were used to construct dose-response curves."	( Voltage clamp analysis of inhibitory synaptic action in crayfish stretch receptor neurons. Adams, PR; Banks, FW; Constanti, A, 1981)	0.26
" A significant correlation was noted between the total dosage and duration of therapy with PHT and the reduction of motor conduction velocity in the posterior tibial nerve."	( Peripheral neuropathy in children on long-term phenytoin therapy. Mochizuki, Y; Motomura, T; Ohkubo, H; Suyehiro, Y; Tanizawa, A, 1981)	0.52
" In contrast, cannabidiol, over a wide dosage range, caused only depression."	( Excitatory and depressant effects of delta 9-tetrahydrocannabinol and cannabidiol on cortical evoked responses in the conscious rat. Karler, R; Turkanis, SA, 1981)	0.26
"0 mg/kg) alone, nor combined treatment with both drugs affected brain GABA level and glutamic acid decarboxylase (GAD) activity at any dosage used."	( Dyphenylhydantoin enhancement of diazepam effects on locomotor activity in mice. Czuczwar, SJ; Kleinrok, Z; Sieklucka-Dziuba, M; Turski, L; Turski, W, 1982)	0.26
" Routine prophylaxis with phenytoin (in a dosage of 5 to 6 mg/kg/day) would seem to be indicated, particularly in high-risk patients and, where possible, this treatment should be started 1 week preoperatively."	( Phenytoin and postoperative epilepsy. A double-blind study. Frewin, DB; Hanieh, A; North, JB; Penhall, RK; Taylor, WB, 1983)	2.01
"Pharmacokinetics as the basis for dosage calculation for acute and subacute treatment of status epilepticus have been discussed."	( Clinical pharmacokinetics of drugs used in the treatment of status epilepticus. Baars, AM; van der Dries, A; van der Kleijn, E; Vree, TB, 1983)	0.27
" Drug levels were monitored throughout with appropriate dosage adjustment; however only 48% of the phenytoin group had plasma levels greater than 40 mumol/l."	( Low risk of late post-traumatic seizures following severe head injury: implications for clinical trials of prophylaxis. Blackwood, DH; Harris, P; Johnson, AL; Kalbag, RM; McQueen, JK, 1983)	0.48
" The aim of this study was to establish a rapid system of drug assay, to report the result, to assess the influence of pathological and clinical factors on the pharmacokinetics of certain drugs, and to use a computer to determine the optimum dosage of drugs."	( Clinical pharmacokinetics: a comprehensive system for therapeutic drug monitoring and prescribing. Bryson, SM; Derkx, FH; Fotheringham, GH; Joel, SE; Kelman, AW; Thomson, AH; Whiting, B, 1984)	0.27
" When binding is altered, the total concentration no longer reflects the amount of pharmacologically active drug in the plasma: this may mislead the clinician into making inappropriate dosage adjustments."	( Free level monitoring of antiepileptic drugs. Clinical usefulness and case studies. Perucca, E, 1984)	0.27
" Conversely, anticonvulsants may influence the dosage requirements of oral anticoagulants by inducing their metabolism."	( Interactions between anticonvulsants and other commonly prescribed drugs. Kutt, H, 1984)	0.27
" Maternal Balb/c mice were dosed by gavage on gestation days 9 through 18 with 0, 20, 40, or 60 mg/kg DPH."	( Humoral immune dysfunction as a result of prenatal exposure to diphenylhydantoin: correlation with the occurrence of physical defects. Chapman, JR; Roberts, DW, 1984)	0.27
" Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction."	( A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Hedges, A; Makki, KA; Perucca, E; Richens, A; Ruprah, M; Wilson, JF, 1984)	0.27
"The objective of this investigation was to study the teratogenic effects of dosage levels and time of administration of three anticonvulsant drugs (carbamazepine [CMZ], sodium valproate [NaV], and diphenylhydantoin [DPH]) on craniofacial development in the CD-1 mouse fetus."	( Teratogenic effects of dosage levels and time of administration of carbamazepine, sodium valproate, and diphenylhydantoin on craniofacial development in the CD-1 mouse fetus. Eluma, FO; Hayes, TG; Paulson, RB; Sucheston, ME, 1984)	0.27
"The Mullen and Foster method was prospectively applied for individualizing phenytoin dosage in 24 epileptic patients."	( Clinical application of the Mullen and Foster method for individualizing phenytoin dosage. Arnetoli, G; Bartoli, C; Donati-Cori, G; Messori, A; Muscas, GC; Silvano, R; Tendi, E; Valenza, T; Zaccara, G; Zappoli, R, 1984)	0.73
" This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values."	( Bioavailability and pharmacokinetics of phenytoin during pregnancy. Chalk, JB; de Wytt, C; Eadie, MJ; Lander, CM; Livingstone, I; Smith, MT; Symoniw, P, 1984)	0.75
" Fifty-one percent of the 53 patients receiving phenytoin were completely controlled at either below or above the 10 to 20 micrograms/ml range, suggesting that individual dosage adjustment is preferably based on clinical judgment rather than numerical limits of published therapeutic ranges."	( Therapeutic plasma levels of phenytoin, phenobarbital, and carbamazepine: individual variation in relation to seizure frequency and type. Haenel, F; Schmidt, D, 1984)	0.81
" There were 780 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 322 patients."	( Steady-state pharmacokinetics of phenytoin from routinely collected patient data. Boenigk, HE; Chiba, K; Dunlop, A; Grasela, TH; Ishizaki, T; Mullen, PW; Rambeck, B; Richens, A; Sheiner, LB; Wadsworth, J, )	0.7
" Our series include 12 patients submitted to carotid TEA in whom cerebral metabolic protection has been obtained by means of DPH at the dosage of 15-17 mg/kg body wt."	( Cerebral protection with diphenylhydantoin during disobliterating surgery of the sovra-aortic branches. Altamura, CA; de Silva, E; Grosso, P; Infuso, L; Massei, R; Ravagnati, L; Robbiati, BR, )	0.13
" Due to the increase in tonic-clonic seizures after the initiation of folic acid (1 mg, orally) the sodium phenytoin dosage was increased by 130 mg until control was achieved."	( Phenytoin and folic acid: individualized drug-drug interaction. Berg, MJ; Fischer, LJ; Rivey, MP; Schottelius, DD; Vern, BA, 1983)	1.92
"A Bayesian feedback technique for predicting phenytoin dosage was compared to other dosing methods."	( Predicting phenytoin dosages using Bayesian feedback: a comparison with other methods. Ludden, TM; Murphy, MJ; Taylor, JW; Yuen, GJ, 1983)	0.92
"his study was performed to determine the potential utility of the cumulation profile of phenytoin during multiple oral dosing and to examine, under ideal conditions, the variability in apparent steady state concentrations."	( Phenytoin cumulation profiles. Bell, RD; Ludden, TM; Yuen, GJ, 1983)	1.93
"5 microM to 100 microM DPH caused parallel, dose-related, rightward displacements of the dose-response curve to CaCl2 in potassium depolarizing solution."	( Diphenylhydantoin inhibition of drug-induced contractions of isolated rat vas deferens: additional evidence for a calcium-blocking action. Calixto, JB; De-Lima, TC, 1983)	0.27
" To maintain a serum level above 10 micrograms per milliliter and abolish seizure activity, it was necessary to carry out repeated serum concentration measurements, administer several loading doses, and administer an unusually large maintenance dose (25 mg per kilogram per day), divided into a short dosing interval (6 hours)."	( High intravenous phenytoin dosage requirement in a newborn infant. Haberkern, CM; Hendeles, L; Neims, AH; Whelan, HT, 1983)	0.61
" Persons taking these drug combinations were identified and matched on the basis of age, sex, body weight, and antiepileptic drug (AED) dosage with persons from the same population who were taking only the AEDs."	( Interaction between phenobarbital and thioridazine. Gay, PE; Madsen, JA, 1983)	0.27
" DPH withdrawal induced a leftward displacement of the dose-response curves obtained for the convulsive effects of both picrotoxin and metrazol and decreased the latency of 3-mercaptopropionic acid-induced seizures."	( Central nervous system supersensitivity and withdrawal from long-term diphenylhydantoin treatment. De-Lima, TC; Palermo-Neto, J, 1983)	0.27
"Over the past few years, numerous pharmacokinetic techniques based on Michaelis-Menten principles have been proposed to individualize PHT dosage and predict plasma levels."	( Comparative analysis of the pharmacokinetic techniques available for individualizing phenytoin dosage. Arnetoli, G; Bartoli, C; Donati-Cori, G; Messori, A; Muscas, GC; Tendi, E; Valenza, T; Zaccara, G, 1983)	0.49
" In epileptic patients, the plasma PHT concentrations were increased when dosage form was changed from the powder to 99%FG-F."	( Comparison of bioavailability for phenytoin products prepared by wet granulation in normal subjects and epileptic patients. Hosaka, A; Ishikawa, N; Kohda, Y; Nakagawa, F; Nishihara, K; Saitoh, Y; Tamura, Z, 1983)	0.54
" The dosage of anticonvulsant drug was found to modify certain test results."	( Compromised hepatic function in dogs treated with anticonvulsant drugs. Baldwin, BH; Bunch, SE; Hornbuckle, WE; Tennant, BC, 1984)	0.27
" For restrictively cleared drugs, displacement from blood proteins will cause only a transient change in free drug concentration and hence in pharmacodynamic response, so that dosage adjustments are rarely necessary."	( Pharmacokinetic consequences of drug displacement from blood and tissue proteins. MacKichan, JJ, 1984)	0.27
" In patients with altered protein binding or an unusual clinical response, free phenytoin determinations appear to be necessary for proper interpretation of total phenytoin levels and rational dosage adjustment."	( The EMIT FreeLevel ultrafiltration technique compared with equilibrium dialysis and ultracentrifugation to determine protein binding of phenytoin. Müller-Vahl, H; Oellerich, M, 1984)	0.7
"In spite of the fact that therapeutic and toxic ranges of phenytoin are well defined, it is still often difficult to calculate an optimal dosage regimen because of the nonlinear saturable kinetics of the drug."	( Influence of bioavailability on the calculated Michaelis-Menten parameters of phenytoin in children. Brand, N; Koren, G; MacLeod, SM, 1984)	0.74
" Potencies were expressed in terms of intraperitoneal dosage and blood and brain concentrations."	( alpha,alpha-Diphenylsuccinimide: evaluation of anticonvulsant and hydrophobic properties. Amato, RJ; Jones, GL; Jones, MF, 1984)	0.27
" Further, for dogs given phenobarbital, there was a sixfold variation between dosage and achieved serum concentration, whereas dogs given primidone manifested even greater variability between dosage and serum concentration."	( Serum concentrations and efficacy of phenytoin, phenobarbital, and primidone in canine epilepsy. Farnbach, GC, 1984)	0.54
" Eleven of the periods occurred after a change in PHT dosage and two after drug withdrawal."	( Phenytoin: the pseudosteady-state phenomenon. Pitlick, W; Porter, RJ; Qu, ZP; Theodore, WH; Tsay, JY, 1984)	1.71
" Pharmacokinetic evaluation was performed on the basis of two different phenytoin serum concentrations obtained on two different dosage regimens."	( Phenytoin-isoniazid interaction: a kinetic approach to management. Ritschel, WA; Witmer, DR, 1984)	1.94
"The application of a Bayesian feedback algorithm for phenytoin (PHT) dosing adjustments was modified empirically to take advantage of measurements of plasma unbound PHT concentrations in the estimation of Km values."	( Use of plasma unbound drug concentrations in adjusting phenytoin doses. Bachmann, K; Forney, R; Voeller, K, 1984)	0.76
" After the first week of life, drug eliminating mechanisms mature and drug dosage requirements often increase dramatically."	( Antiepileptic drug utilization in pediatric patients. Dodson, WE, 1984)	0.27
" However, no adjustment of phenytoin dosage is warranted, unless clinically indicated, since the free phenytoin levels remain unchanged."	( Interaction between phenytoin and valproate. Beran, RC; Sansom, LN; Schapel, GJ, 1980)	0.88
" In practice, blood level determinations have their special value for the detection of the intake of a wrong dosage of the drugs as well as bland anticonvulsant intoxications."	( [Serum anticonvulsant levels in therapy-resistant epileptics]. Broeker, H; Müller, D; Müller, J; Walther, H, 1980)	0.26
"The incidence of malformations in fetal mice exposed to phenytoin depends on drug dosage and the strain of mice."	( Teratogenic effects of anticonvulsants. Paulson, GW; Paulson, RB, 1981)	0.51
" A graphic analysis of the relationship between plasma concentration and dosage is proposed as practical method of assessing compliance, because it appears to be both simple and reliable, and therefore suitable for routine use."	( Phenytoin therapy for epileptic children: evaluation of salivary and plasma concentrations and of methods of assessing compliance. Bircher, J; Küpfer, A; Rüdeberg, A; Vassella, F; Zysset, T, 1981)	1.71
" Even with the dosage regimen of 20 mg of drug/kg given TID orally, therapeutic plasma concentrations could only be maintained for the first 2 or 3 days of treatment; these subsequently decreased to ineffective concentrations during the 1st week of treatment."	( Clinical pharmacokinetics of phenytoin in the dog: a reevaluation. Frey, HH; Löscher, W, 1980)	0.55
"Following replacement of diphenylhydantoin (DPH) medication by a DPH preparation of different manufacture in a 41 years old woman the patient developed in spite of identical dosage clinical symptoms of overdosage which could be confirmed by EEG and determination of serum levels."	( [Diphenylhydantoin intoxication following the exchange of seemingly equal DPH-preparations (author's transl)]. Klingler, D; Nitsche, V; Schmidbauer, H, 1981)	0.26
" The patients' dose-response curves resembled the response of control cells in which epoxide hydrolase (a detoxification enzyme for arene oxides) was inhibited."	( Predisposition to phenytoin hepatotoxicity assessed in vitro. Blake, DA; Goldstein, DA; Gordon, GB; Herlong, HF; Spielberg, SP, 1981)	0.6
" This would be a manifestation of an independent Phenytoin effect in the high toxic dosage respectively in withdrawal."	( [EEG in phenytoin intoxication (author's transl)]. Mayr, N; Wessely, P, 1981)	0.95
" Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements."	( Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy. Hamshaw-Thomas, A; Knott, C; Reynolds, F, 1982)	2
"In view of the observed variation of valproic acid (VPA) free fraction (fp) during a dosing interval and the competitive binding effect of free fatty acids (FFA) in vitro, this study was designed to address the existence of diurnal variations in the fp of VPA."	( Diurnal oscillations in plasma protein binding of valproic acid. Levy, RH; Ojemann, LM; Patel, IH; Venkataramanan, R; Viswanathan, CT, 1982)	0.26
" Fortunately, the drugs used by the majority of these patients are readily measured in plasma, and in most cases the plasma concentration is a valid measure of the appropriateness of the dosage of drug administered."	( Antiepileptic therapeutic drug monitoring. Cohan, SL, 1981)	0.26
"The authors studied antipyrine disposition before and after delivery in 4 epileptic women whose anticonvulsant plasma level per dosage ratio was lowered during pregnancy, and compared the results to those found in nonpregnant women undergoing antiepileptic treatment (N = 6) and healthy women (N = 6)."	( Antipyrine disposition in relation to lowered anticonvulsant plasma level during pregnancy. Chiba, K; Ishizaki, T; Nakazawa, Y; Tabuchi, T; Wagatsuma, T, 1982)	0.26
" However, displacement alone, unlike induced metabolism, should not affect the drug's dose-response relationship."	( Drug interactions with valproic acid. Koch, KM; Levy, RH, 1982)	0.26
" Each compound was administered by intravenous single dose injection, dosage being 1 mg/kg for propranolol, 10 mg/kg for phenytoin, and 3,5 mg/kg for lidocain."	( [Pharmacokinetics of propranolol, phenytoin and lidocaine in hypercholesterolemic rabbits]. Albin, H; Pehourcq, F; Ploux, D; Vinçon, G, )	0.62
"f values of both dosage forms at steady-state were in good correspondence to the observed values of PHT excreted in feces."	( Bioavailability of phenytoin on single and multiple oral doses of two dosage forms in normal subjects. Isozaki, S; Kohda, Y; Nakagawa, F; Nishihara, K; Saitoh, Y; Tamura, Z, 1983)	0.59
" Because of these physicochemical properties, phenytoin is subject to erratic bioavailability in a variety of dosage forms both in its acidic as well as sodium salt forms."	( Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs. Roberts, RD; Stella, VJ; Yamaoka, Y, 1983)	0.9
" Patients receiving anticonvulsant medication must make no change in drug dosage without medical guidance because of the risk of this catastrophic consequence."	( Anticonvulsants and neurogenic pulmonary edema. Mandel, S; Paschall, R, 1983)	0.27
"The dissolution profiles of 11 commercially available papaverine, phenytoin, and sulfisoxazole dosage forms were determined using a dissolution simulator."	( In vivo-in vitro correlations with a commercial dissolution simulator II: papaverine, phenytoin, and sulfisoxazole. Meyer, MC; Yau, MK, 1983)	0.73
" Patients receiving more than one phenytoin dosage regimen had significant but weak correlations between Vmax and Km."	( Phenytoin dosage requirements and pharmacokinetic variables. Berg, MJ; Ludden, TM; Lyon, LW; Murphy, MJ; Perry, PJ; Taylor, JW, )	1.85
" Oral dosage regimens were calculated on the basis of a dosing interval of 8 h to provide average serum steady-state concentrations of 5 and 10 micrograms/ml for phenytoin."	( Pharmacokinetics of phenytoin (diphenylhydantoin) in horses. Beech, J; Kowalczyk, DF, 1983)	0.79
" The radiation dosage in each group was equal to 1702 ret."	( The Cambridge glioma trial of misonidazole and radiation therapy with associated pharmacokinetic studies. Bleehen, NM, 1980)	0.26
" Fifty-three patients were tested using the EMIT assay system, and a questionnaire was used to compare the physicians' choice of drug dosage and appointment interval before and after each patient result was available."	( Evaluation of the provision of rapid drug plasma assays in an outpatient anticonvulsant clinic. Fullinfaw, R; King, J; Marty, J; Trembath, P; Tuckett, R, 1981)	0.26
"5%) cases without correlation with the dosage (D in mg/kg)."	( Comparative study of bioavailabilities of different phenytoin preparations. Fukuyama, Y; Goto, T; Kitahara, H, 1982)	0.51
"0% at discharge) versus polytherapy; degree of correspondence between recommended and observed dosage regimens (undertreatment being a more common problem than excessive dosing); and reporting of side effects."	( Quality of care of epilepsy in Italy: multi-hospital survey of diagnosis and treatment of 1104 epileptic patients. Beghi, E; Sasanelli, F; Spagnoli, A; Tognoni, G, 1982)	0.26
" The relationship between plasma phenytoin, body weight, and daily dosage of the drug were explored, and the data were analysed by multiple regression."	( Prediction of phenytoin dosage in epilepsy using multiple linear regression. Gray, SP, 1982)	0.91
" The modal dosage was 50 mg 3-times daily and treatment ranged between 6 to 19 weeks."	( The use of phenytoin in neurotic disorders treated in general practice. Haward, LR, 1982)	0.65
" Caffeine can shift the dose-response curve of chlorpromazine-inhibited sperm motility to right."	( Effects of chlorpromazine and other drugs acting on the central nervous system on human sperm motility. Chaput de Saintonge, DM; Hong, CY; Turner, P, 1982)	0.26
" The DPH/HPPH ratios in plasma specimens showed excellent correlation with the plasma half-lives of DPH and average steady-state levels, suggesting that this ratio could provide guidance in the selection of optimum dosage regimens for problem patients."	( Phenytoin metabolism in subjects with long and short plasma half-lives. Buchanan, RA; Chang, T; Dill, WA; Glazko, AJ; Peterson, FE; Smith, TC, 1982)	1.71
" The subjects then underwent dosage adjustment utilizing the slow release formulation, and estimates of their Michaelis-Menten parameters thus obtained were utilized in calculating the relative bioavailabilities."	( Rapid and slow release phenytoin in epileptic patients at steady state: assessment of relative bioavailability utilizing Michaelis-Menten parameters. Gumnit, RJ; Leppik, IE; Pepin, SM; Sawchuk, RJ, 1982)	0.57
" The concentration-dependence of the t50% provided the basis for less frequent dosing than one would expect from previous studies of PHT half-life in children with low concentrations."	( Phenytoin elimination in childhood: effect of concentration-dependent kinetics. Dodson, WE, 1980)	1.7
" Once two phenytoin serum levels were obtained on two different dosage regimens, a table of future doses and predicted serum levels was calculated and plotted on a graph."	( Predicting individual phenytoin serum levels of patients seen in a private office practice. Gonzalez, MA; Robinson, FC; Warner, RN, 1981)	0.98
" In patients with predisposing factors to postoperative seizures, anticonvulsant drugs should be administered before or immediately following craniotomy in adequate dosage to rapidly achieve and maintain effective plasma levels."	( Seizures following intracranial surgery: incidence in the first post-operative week. Matthew, E; Odusote, K; Sherwin, AL; Stratford, JG; Welner, SA, 1980)	0.26
" Six methods of predicting phenytoin dosage or plasma concentrations--one equation, two nomograms, and three graphs--were compared to actual phenytoin doses and corresponding steady-state serum levels."	( Clinical utility of six methods of predicting phenytoin doses and plasma concentrations. Bruni, J; Murphy, JE; Stewart, RB, 1981)	0.82
" Methadone dosing adjustments should be anticipated when phenytoin is initiated or discontinued in methadone-maintained patients."	( Phenytoin-induced methadone withdrawal. Benowitz, NL; Jaffery, NF; Kreek, MJ; Pond, SM; Tong, TG, 1981)	1.95
" The concentration of phenytoin and IgA showed little variation during the dosage interval."	( Phenytoin and IgA concentrations in plasma and saliva in epileptic children. Falk, O; Modéer, T; Rane, A; Tomson, G, 1981)	2.02
" The criteria specified the indication for each drug, performance data, and dosage adjustments with SDA results."	( Effect of pharmacist intervention on the use of serum drug assays. Birmingham, PH; Cohen, SS; Levin, B, 1981)	0.26
"Three programs are presented which have been developed to simulate conditions encountered in the pharmacokinetic adjustment of dosage regimens."	( A package of computer programs designed to simulate pharmacokinetic monitoring of drug therapy. Sullivan, TJ; Wunderley, DJ, 1980)	0.26
" Noncompliant patients were characterized as having a longer duration of epilepsy, more complicated dosage regimens, and more changes in medication."	( Determinants of compliance in epileptic outpatients. Bryant, SG; Ereshefsky, L, )	0.13
"Most previously suggested methods for predicting phenytoin dosage from steady-state drug levels (Cpss) measured in the clinical setting fail to fully exploit all relevant (population) information."	( Predicting individual phenytoin dosage. Follath, F; Muir, KT; Sheiner, LB; Vozeh, S, 1981)	0.83
" These sites appear to be interdependent since analysis of the shift in the DPH dose-response curve by PTX and vice versa, showed neither truly non-competitive nor competitive interaction."	( On the action of the anticonvulsant 5,5-diphenylhydantoin and the convulsant picrotoxin in crayfish stretch receptor. Aickin, CC; Deisz, RA; Lux, HD, 1981)	0.26
" In the case of clinial manifestation of side effects it might be concluded that the dosage of DPH should be reduced."	( Antiepileptic drug levels and side effects in man. Oettinger, B; Richter, K, 1980)	0.26
" Data from a drug surveillance study showed that 10 of 32 patients had a significant change in plasma digoxin concentration after admission to hospital, indicating deviations in compliance with the dosage regimen prior to hospitalisation."	( Digoxin and Phenytoin analyses as part of consultations in clinical pharmacology: a study on the use of drugs. Bergman, U; Rane, A; Sjöqvist, F; Wiholm, BE, 1981)	0.64
" Saliva samples were easily obtained and the measured concentrations were a valuable guide to drug dosage during the treatment period."	( Monitoring of phenobarbitone and phenytoin therapy in small children by salivary samples. Bacon, CJ; Hierons, AM; Mucklow, JC; Rawlins, MD; Webb, JK, 1981)	0.54
"The effects of long term, low dosage anticonvulsant drug therapy on the vitamin D and folacin status of young children was studied."	( Folic acid and vitamin D status of young children receiving minimal anticonvulsant drug therapy. Bailey, LB; Enneking-Ivey, O; Gawley, L; Hananian, J; Hurd, R, 1981)	0.26
"A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated."	( Single point estimation of phenytoin dosing: a reappraisal. Gibaldi, M; Godolphin, W; Koup, JR, 1981)	0.82
" These observations suggest that dosage regimen adjustment of phenytoin based on the averaged Vmax in a given pediatric age group rather than the Km is recommended for a particular patient with inadequate therapeutic control of seizure or toxicity of this drug."	( Apparent Michaelis-Menten kinetic parameters of phenytoin in pediatric patients. Chiba, K; Ishizaki, T; Minagawa, K; Miura, H, 1980)	0.76
" A method for individualizing the dosage regimen of DPH for each patient was evaluated retrospectively."	( Michaelis-Menten pharmacokinetics of diphenylhydantoin and application in the pediatric age patient. Chiba, K; Ishizaki, T; Minagawa, K; Miura, H, 1980)	0.26
"Four methods for estimating dosage regimens for drugs exhibiting non-linear pharmacokinetic behavior (e."	( Using pharmacokinetics in drug therapy. VI: Comparing methods for dealing with nonlinear drugs like phenytoin. Schumacher, GE, 1980)	0.48
"Recent developments of clinical pharmacology show that in particular circumstances the determination of the plasmatic levels of drugs seems to be the best way to insure the best dosage schedules for each patient."	( Clinical pharmacokinetics: the pharmacological monitoring of plasmatic levels in therapy. Bonora, MR; Guaglio, R; Rondanelli, R; Terzoni, PA, 1980)	0.26
"A programmable calculator procedure for the determination of individualized phenytoin dosage regimens is described."	( Individualizing phenytoin dosage regimens using a programmable calculator. Ng, PK, 1980)	0.84
"We describe a procedure for determining 2-ethyl-2-phenylmalonamide (I) in serum of epilepsy patients dosed with primidone (II) for seizure control, by extracting the sample with chloroform under basic conditions, with use of an internal standard, 2-ethyl-2-(p-tolyl)malonamide, and without derivative formation."	( Monitoring 2-ethyl-2-phenylmalonamide in serum by gas-liquid chromatography: application to retrospective study in epilepsy patients dosed with primidone. Haidukewych, D; Rodin, EA, 1980)	0.26
" In order to test the validity of FEAD as an absence seizure model, the present experiments determined dose-response relationships for the suppression of FEAD by six antiepileptic drugs with established clinical profiles."	( Flash-evoked afterdischarge in rat as a model of the absence seizure: dose-response studies with therapeutic drugs. Burnham, WM; King, GA; Livingston, KE, 1980)	0.26
" Within the therapeutic range, small increments in dosage resulted in large increments in plasma DPH levels, and in the postpartum period high levels of DPH were encountered if the dosage was not reduced."	( Phenytoin metabolism in pregnancy. Emery, MG; Kochenour, NK; Sawchuk, RJ, 1980)	1.7
"5 micrograms/ml in the dosage range of 50 and 75 mg/kg, respectively), significantly impaired learning and memory in rats."	( Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels. Lakshmana, MK; Pradhan, N; Sudha, S, 1995)	0.73
" This anti-MES activity is achieved with nontoxic doses, with the optimal effect recorded in rats dosed orally with anti-MES ED50 and protective index (PI) values of 25."	( Comparative anticonvulsant activity and neurotoxicity of 4-amino-N-(2,6-dimethylphenyl)phthalimide and prototype antiepileptic drugs in mice and rats. Bailleux, V; Hamoir, G; Nuyts, JP; Poupaert, JH; Stables, JP; Vallée, L; Vamecq, J, 1995)	0.29
" After 1-month observation, the patients entered a 7-month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/kg/day, to be increased to 60 and 80 mg/kg/day at 2-month intervals if seizures persisted."	( Efficacy and tolerability of vigabatrin in children with refractory partial seizures: a single-blind dose-increasing study. Buti, D; Cianchetti, C; Dalla Bernardina, B; Fontana, E; Fusco, L; Galeone, D; Gnanasakthy, A; Iudice, A; Torelli, D; Vigevano, F, 1995)	0.29
" The peak effect was reached 1 h after dosing the monoglyceride compared to 2 h after application of phenytoin itself."	( Bioavailability and anticonvulsant activity of a monoglyceride-derived prodrug of phenytoin after oral administration to rats. Lambert, DM; Poupaert, JH; Scriba, GK, 1995)	0.73
" There were 258 steady-state serum phenytoin concentrations and associated dosage (mg."	( [NONMEM approach for estimating population pharmacokinetic parameters of phenytoin in Chinese epileptics]. Cai, MH; Chen, G; Chu, XM; Rui, JZ, 1995)	0.8
"To develop simple clinical rules for dosing phenytoin (PHT) using computer simulations, then to test the rules for accuracy and safety on actual patient data."	( Clinical rules for phenytoin dosing. Privitera, MD, 1993)	0.88
" A computerized dosing program calculated pharmacokinetic parameters using Bayesian methodology, then predicted how many patients were likely to reach potentially toxic PHT plasma concentrations when their daily dosage was increased by 30, 50, or 100 mg."	( Clinical rules for phenytoin dosing. Privitera, MD, 1993)	0.61
" Patients for the computer simulation were from three sources: (1) patients who had an initial PHT plasma concentration < 10 micrograms/mL and required a dosage increase; (2) patients admitted to the hospital for PHT intoxication; and (3) patients who required consultations specifically for PHT dosing."	( Clinical rules for phenytoin dosing. Privitera, MD, 1993)	0.61
"Successful dosing rules allowing fewer than ten percent of resulting plasma concentrations in the test group to exceed 25 micrograms/mL."	( Clinical rules for phenytoin dosing. Privitera, MD, 1993)	0.61
" The resulting dosing rules were: increase the dosage by 100 mg/d if the initial plasma concentration was < 7 micrograms/mL; increase the dosage by 50 mg/d if the initial plasma concentration is 7 to < 12 micrograms/mL; increase the dosage by 30 mg/d if the initial plasma concentration is > or = 12 micrograms/mL."	( Clinical rules for phenytoin dosing. Privitera, MD, 1993)	0.61
"The proposed dosing rules are a simple method for clinicians to estimate PHT dosage changes and appear to be safe and accurate when applied retrospectively to actual patient data."	( Clinical rules for phenytoin dosing. Privitera, MD, 1993)	0.61
" An understanding of the underlying pharmacokinetic processes, including the need of most elderly patients for lower doses and longer dosing intervals, permits more effective management of therapy and reduces the risk for adverse reactions."	( Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Cloyd, JC; Lackner, TE; Leppik, IE, 1994)	0.29
" Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration."	( Flunarizine for treatment of partial seizures: results of a concentration-controlled trial. Drake, ME; Mikati, M; Olson, L; Pellock, JM; Pledger, GW; Sackellares, JC; Sahlroot, JT; Treiman, DM; Tsay, JY; Wright, FS, 1994)	0.29
"Utilization of the solid mass containing phenytoin, sodium caseinate and microcrystalline cellulose (MCC) as a new dosage form for the elderly was studied."	( Release profiles of phenytoin from new oral dosage form for the elderly. Hanawa, T; Sugihara, M; Watanabe, A; Yamamoto, K, 1994)	0.88
"6%) and, when method 3 is used, may offer useful information for the adjustment of dosage schedules."	( Predictive performance of two phenytoin pharmacokinetic dosing programs from nonsteady state data. Dominguez-Gil, A; García, MJ; Gavira, R; Santos Buelga, D, 1994)	0.58
" Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments."	( Pharmacokinetics of phenytoin in routine clinic patients in Malaysia. Chand, P; Ismail, R; Rahman, AF, 1994)	0.61
"Phenytoin sodium was microencapsulated with ethylcellulose (EC) by a coacervation-phase separation method from ethyl acetate solution to develop a prolonged release dosage form of phenytoin."	( Sustained release of phenytoin following the oral administration of phenytoin sodium/ethylcellulose microcapsules in human subjects and rabbits. Karakasa, I; Kenmotsu, H; Sekikawa, H; Shibata, M; Takada, M; Yagi, N, 1994)	2.05
" Consequently, the controlled trial was designed to account for this interaction by reducing the phenytoin dosage by approximately 20% during the felbamate treatment period and using matching placebo capsules to maintain the blind."	( Dosage adjustments in response to monitored plasma concentrations: can unblinded staff adhere to objective criteria? Pledger, GW; Sahlroot, JT, 1994)	0.51
" Overall, the data provide no support for the view that the degree of discriminability of a drug is an indicator of potential state-dependency effects and is restricted only to the dosage high enough to produce noticeable intoxication."	( Phenytoin and phenobarbital: a comparison of their state-dependent effects. Karanth, KS; Kumar, KB; Ramalingam, S, 1994)	1.73
" Dosage was kept constant unless poor seizure control prompted an increase."	( Epilepsy and pregnancy: a prospective study of seizure control in relation to free and total plasma concentrations of carbamazepine and phenytoin. Ekqvist, B; Lindbom, U; Sundqvist, A; Tomson, T, )	0.33
" The frequency of congenital defects in PHT-treated animals was dosage dependent, ranging from 7 to 55%."	( Protection from phenytoin-induced congenital malformations by coadministration of the antiepileptic drug stiripentol in a mouse model. Finnell, RH; Kerr, BM; Levy, RH; Steward, RL; van Waes, M, )	0.48
" CBZ-CR and PHT were administered to 42 adult patients (21 each) at a dosage of 20 mg/kg with a minimum and maximum dosage of 1,200 and 1,600 mg in patients weighting < 60 and > 80 kg, respectively."	( Acute oral loading of carbamazepine-CR and phenytoin in a double-blind randomized study of patients at risk of seizures. Kruger, AJ; Müller, FO; Rabie, W; Schall, R; Van Der Meyden, CH, )	0.39
" Ten weeks later she was normocalcemic, and the calcitriol dosage was reduced."	( Abnormal bone mineral metabolism after long-term anticonvulsant treatment. Alderman, CP; Hill, CL, 1994)	0.29
" Median AUCs of CBZ, VPA and PHT during a dosage interval did not differ significantly after treatment with OXC and placebo."	( A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Blacklaw, J; Brodie, MJ; Connelly, D; Forrest, G; Gillham, RA; McKee, PJ; Walker, SM, 1994)	0.5
" Serum drug concentration monitoring will be necessary to determine the optimal dosage regimen."	( Effect of continuous hemofiltration on phenytoin elimination. Kronfol, NO; Lau, AH, 1994)	0.56
" We collected dosage interval urine samples from three groups of 10 valproate patients: (1) valproate monotherapy, (2) valproate with carbamazepine, and (3) valproate with phenytoin."	( Interaction between valproate and branched-chain amino acid metabolism. Acheampong, AA; Anderson, GD; Levy, RH, 1994)	0.48
"The objective of this study was to assess the feasibility of giving phenytoin to a group of mild preeclamptic women in a universal dosing scheme comparable to that typical of magnesium sulfate administration."	( A simplified phenytoin regimen for preeclampsia. Cunningham, FG; DePalma, RT; Leveno, KJ; Lucas, MJ; Person, D; Peters, MT, 1994)	0.89
" Observed statistical differences in total phenytoin concentrations can be clinically important for making dosage adjustments, especially in patients undergoing nonlinear elimination."	( Influence of serum separator tubes on total and free phenytoin concentrations and dosages. Cai, WM; Chandler, MH; Leader, WG; Porter, WH, 1993)	0.8
"Four in vitro administration techniques were evaluated to determine which method would produce the least amount of phenytoin lost with long-term (14 days) dosing of Dilantin Kapseals (100 mg) or Dilantin suspension 125 mg/5 mL (92 mg) through 20 French percutaneous endoscopic gastrostomy Pezzer catheters."	( Phenytoin recovery from percutaneous endoscopic gastrostomy Pezzer catheters after long-term in vitro administration. Allen, LV; McGoodwin, PL; Seifert, CF, )	1.78
" 9 out of 10) patients showing phenytoin levels < 5 ug/ml inspite of phenytoin dosage of > 300 mg/d and history of good compliance were found to be noncompliant."	( Compliance monitoring in epileptic patients. Chandra, RS; Dalvi, SS; Karnad, PD; Kshirsagar, NA; Shah, PU, 1993)	0.57
" Doubling the daily carbamazepine dosage did not yield quantifiable serum concentrations."	( Unmasking the significant enzyme-inducing effects of phenytoin on serum carbamazepine concentrations during phenytoin withdrawal. Abou-Elkair, M; Chapron, DJ; LaPierre, BA, 1993)	0.54
" The results suggest that no overall dosage adjustments are required when switching from one brand to the other."	( Comparison of the effectiveness of two oral phenytoin products and chronopharmacokinetics of phenytoin. Morton, DJ; Petker, MA, 1993)	0.55
" Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled."	( Valproate-induced coma: case report and literature review. Clavería, LE; Coria, F; Duarte, J; Fernandez, E; Macias, S, 1993)	0.29
" The t 1/2 and AUC values of PB were significantly increased by ZNS coadministration, and a significant decrease in the Vd/F value of PHT was observed after multiple dosing of ZNS."	( Pharmacokinetic interaction of zonisamide in rats. Effect of zonisamide on other antiepileptics. Fukuchi, H; Kimura, M; Kimura, Y; Kitaura, T; Miyake, K; Tanaka, N, 1993)	0.29
" After an 8-week baseline period, a single-dose pharmacokinetic study was performed for each patient to calculate a loading dose and maintenance dosage necessary to achieve a target plasma FNR concentration of 30 ng/ml."	( Increasing plasma concentration tolerability study of flunarizine in comedicated epileptic patients. Cereghino, JJ; DeGiorgio, C; Pledger, GW; Treiman, DM; Tsay, JY, )	0.13
"Physicochemical factors influencing the release of phenytoin sodium from slow-release dosage forms were studied."	( Influence of pH on release of phenytoin sodium from slow-release dosage forms. Jarowski, CI; Serajuddin, AT, 1993)	0.83
" Drug was most often given on a fixed dosing schedule with additional medication "as needed" (52% of the programs)."	( Alcohol withdrawal: a nationwide survey of inpatient treatment practices. Friedman, LS; Mayo-Smith, MF; Saitz, R, 1995)	0.29
" Lesion severity was then compared statistically to phenytoin dosage and drug concentrations as well as to other clinical and laboratory parameters."	( Phenytoin as a risk factor in gingival hyperplasia. Kolínová, M; Patzelová, V; Perlík, F; Zvárová, J, 1995)	1.98
" The plasma phenytoin concentration-time profile was determined on Day 7 before the start of sertraline or placebo dosing and at the end of dosing on Day 24."	( Absence of effect of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin. Cross, M; Muirhead, DC; Rapeport, WG; Wesnes, K; Williams, SA, 1996)	0.9
" TPM was added to the baseline antiepileptic drug (AED) at a dosage of up to 800 mg/day, after which the baseline drug was discontinued, when possible."	( Drug interaction profile of topiramate. Bourgeois, BF, 1996)	0.29
" Despite differences of the phenytoin plasma concentrations all three compounds approximately doubled the AUC compared with the dosing of phenytoin itself."	( Bioavailability of phenytoin following oral administration of phenytoin-lipid conjugates to rats. Lambert, DM; Poupaert, JH; Scriba, GK, 1995)	0.91
"To longitudinally evaluate unbound and total serum phenytoin concentrations during intravenous phenytoin maintenance dosage and to determine the relationship among phenytoin protein binding, serum albumin, and unbound fatty acid concentrations in patients with head injuries during intensive care unit (ICU) and convalescent care."	( Phenytoin protein binding and dosage requirements during acute and convalescent phases following brain injury. Christie, JM; Ehresman, DJ; Eyer, SD; Markowsky, SJ; Skaar, DJ, 1996)	1.99
" The high dosage requirements and subtherapeutic unbound phenytoin concentrations observed during acute care are best explained by increased metabolism."	( Phenytoin protein binding and dosage requirements during acute and convalescent phases following brain injury. Christie, JM; Ehresman, DJ; Eyer, SD; Markowsky, SJ; Skaar, DJ, 1996)	1.98
" Aggressive dosing of phenytoin may be required to achieve therapeutic concentrations in patients who are concurrently receiving chemotherapy and/or dexamethasone, especially in patients who fall outside the predictive pharmacokinetic model for phenytoin."	( Possible interaction involving phenytoin, dexamethasone, and antineoplastic agents: a case report and review. Gattis, WA; May, DB, 1996)	0.89
" This investigation sought to elucidate both the incidence and nature of acute intravenous phenytoin toxicity in emergency department patients, and to identify any demographic, clinical, or dosing associations with toxicity, by analyzing a retrospective case series over 3 years in a municipal teaching hospital."	( Association of intravenous phenytoin toxicity with demographic, clinical, and dosing parameters. Binder, L; Cuetter, A; Parker, D; Trujillo, J, 1996)	0.81
" Thirty-six adult epileptic patients who had been receiving phenytoin for greater than 6 months without a recent change in dosage were assessed for signs of periodontal disease and gingival overgrowth."	( Plasma and saliva concentrations of phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin in relation to the incidence and severity of phenytoin-induced gingival overgrowth in epileptic patients. Ball, DE; Kamali, F; McLaughlin, WS; Seymour, RA, 1996)	0.81
" The daily dosage of each drug was held constant during treatment of the obesity."	( Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study. Ashikari, Y; Chiba, S; Kodama, Y; Kuranari, M; Sakata, T; Takeyama, M, 1996)	0.66
" A drug concentration, however, can only be regarded as a guide around which to alter the dosage according to the patient's clinical condition."	( Optimisation of antiepileptic drug therapy. The importance of serum drug concentration monitoring. Yukawa, E, 1996)	0.29
" The aim of this study was to evaluate which dosage of PHT can maintain the therapeutic range in the early postoperative period."	( Peri-operative prophylaxis with phenytoin: dosage and therapeutic plasma levels. Boselli, L; Levati, A; Savoia, G; Tommasino, C; Zoppi, F, 1996)	0.58
" When PB in the dosage of 30-60 mg/d was used in combination with PHT the above mentioned changes were not observed."	( Brainstem auditory evoked potentials in epileptics on different anti-epileptic drugs. Gupta, HL; Mukhopadhyay, S; Panjwani, U; sel Vamurthy, W; Singh, SH; Thakur, L, 1996)	0.29
" In the majority of those patients for whom dosage reduction, or drug discontinuation or substitution is not possible, and for whom prophylactic measures have failed, surgical excision of gingival tissue remains the only treatment of choice."	( Gingival enlargement induced by drugs. Berini, L; Brunet, L; Farré, M; Mendieta, C; Miranda, J, 1996)	0.29
" Dosing of fosphenytoin uses phenytoin equivalents (PE) to minimize dosage errors when converting from the conventional formulation."	( Fosphenytoin: a novel phenytoin prodrug. Boucher, BA, )	1.11
" We studied the PHT dose-response curve for serum PHT and glucose concentrations and several physiological variables."	( Phenytoin-induced hyperglycaemia may confound rat cerebroprotection models. Newman, GC; Qi, H, )	1.57
" The population pharmacokinetic parameters of phenytoin will be useful for designing dosage regimens in epileptic patients."	( Population pharmacokinetics of phenytoin in Japanese patients with epilepsy: analysis with a dose-dependent clearance model. Furusho, K; Hashimoto, Y; Hattori, H; Inui, K; Koue, T; Odani, A; Otsuki, Y; Takano, M; Takayanagi, K; Yasuhara, M, 1996)	0.84
" The dosage is expressed as phenytoin sodium equivalents (PE)."	( Safety of fosphenytoin sodium. Benezra, DA; Fierro, LS; Savulich, DH, 1996)	0.96
" All patients received a drug dosage to ensure adequate plasma concentration and satisfactory seizure control."	( The effect of chronic carbamazepine, valproic acid and phenytoin medication on the periodontal condition of epileptic children and adolescents. Borowicz-Andrzejewska, E; Borysewicz-Lewicka, M; Galas-Zgorzalewicz, B; Zgorzalewicz, M, )	0.38
" To date, apart from anecdotal case reports or studies involving a very limited number of patients, few data regarding the dosing and usage of medications in neonates and paediatric patients are available in the literature."	( [Development of a practical guide for utilization of injectable drugs in neonatology and in pediatrics]. Bressolle, F; Courrege, C; Kinowski, JM; Poujol, H; Veillet, B, )	0.13
"To underscore the need for caution when making dramatic changes in phenytoin dosing, and to report a possible ciprofloxacin interaction in which failure of seizure control led to inappropriately high phenytoin dosing and subsequent intoxication."	( Hazards of doubling phenytoin dose in the face of an unrecognized interaction with ciprofloxacin. Pollak, PT; Slayter, KL, 1997)	0.86
" In response to the 80% decline in phenytoin concentration, the dosage was gradually titrated upward to produce a serum concentration of 12."	( Hazards of doubling phenytoin dose in the face of an unrecognized interaction with ciprofloxacin. Pollak, PT; Slayter, KL, 1997)	0.9
" In a conscientious effort to titrate phenytoin concentrations back to therapeutic values, the issue as to why this required such a dramatic change in dosage was ignored."	( Hazards of doubling phenytoin dose in the face of an unrecognized interaction with ciprofloxacin. Pollak, PT; Slayter, KL, 1997)	0.89
" Irrespective of the drug used, optimal clinical management requires individualization of dosage and dosing schedules based on careful evaluation of clinical response and sound knowledge of the pharmacokinetics and interaction potential of the individual compounds."	( Established antiepileptic drugs. Perucca, E, 1996)	0.29
" In the second part, seven male and seven female patients with seizures with informed consent received these calculated dosage regimens."	( Single oral loading dose of phenytoin: a pharmacokinetics study. Kaojarern, S; Mokkhavesa, C; Phuapradit, P; Ratanakorn, D, 1997)	0.59
" Plasma concentration profiles of PHT, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single and multiple dosing with remacemide hydrochloride."	( Mutual interaction between remacemide hydrochloride and phenytoin. Brodie, MJ; Girvan, J; Jamieson, V; Jones, T; Leach, JP; Richens, A, 1997)	0.54
" We proposed a prophylactic treatment with endovenous PHT consisting of two infusions of PHT (mean dosage of 18 mg/kg; mean time of 1 hr) perioperatively and during the first postoperative day."	( Early postoperative seizures and endovenous phenytoin. Preliminary clinical data. Baratta, P; Bello, L; Ceccarelli, G; De Santis, A; De Silva, E; Signoroni, G; Songa, V; Spagnoli, D; Villani, RM, )	0.39
" Initial screening in mice dosed intraperitoneally and rats dosed orally indicated that 4-AEPB is active against maximal electroshock-induced seizures (MES), but does not protect animals against subcutaneous pentylenetetrazole (sc Ptz)-induced seizures."	( Anticonvulsant and neurotoxicological properties of 4-amino-N-(2-ethylphenyl)benzamide, a potent ameltolide analogue. Bourhim, M; Diouf, O; Lambert, DM; Poupaert, JH; Stables, JP; Vamecq, J, 1997)	0.3
" Thus, the dosage of digitoxin appears to be fully compensated during concomitant use of phenobarbital, but obviously deserves attention during concomitant use of phenytoin or carbamazepine."	( [Serum digitoxin in concomitant use of antiepileptics in routine therapy]. Aass, H; Johannessen, SI; Osnes, JB; Skomedal, T; Stokke, KT, 1997)	0.49
"Phenytoin dosing is often difficult in a clinical situation because of the non-linear nature of phenytoin metabolism at therapeutic plasma concentrations."	( Single-point phenytoin dosage predictions in Singapore Chinese. Chan, E, 1997)	2.11
" In rats dosed orally, aminoretrobenzamides were less active in the MES test than in mice dosed intraperitoneally."	( [Rational conception, synthesis and evaluation of phenytoinergic potential anticonvulsants. A series ofretrobenzamides: N-(nitrophenyl) benzamides and N-(aminophenyl) benzamides]. Bourhim, M; Kanyonyo, MD; Lambert, DM; Poupaert, JH; Stables, JP; Vamecq, J, )	0.38
"Phenytoin toxicity occurred in an older man who received a dosage of 300 mg/day."	( Phenytoin toxicity in an older patient with slow metabolism and atypical presentation. Long, LD; Meyer, RP; Pennypacker, LC; Pitner, JK, )	3.02
"26), daily dosage (8."	( Comparison of phenytoin serum concentrations in premature neonates following intravenous and oral administration. Frey, OR; Probst, W; von Brenndorff, AI, 1998)	0.66
" No significant difference was found in phenytoin dosage per kg of body weight, protein intakes, calcium, magnesium and sodium per 24 hours between the means for the two groups."	( Serum phenytoin levels of patients on gastrostomy tube feeding. Faraji, B; Yu, PP, 1998)	1.05
"The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed."	( Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings. Altavela, JL; Doak, KK; Dunnigan, KJ; Haas, CE; Huntress, J; Reiser, JR; Reiss, RA, )	0.46
" These data suggest that the response of juvenile Purkinje cells is dependent upon the dosage of the antiepileptic drug because of morphological alterations as well as a misrouting of previously established connections."	( Phenytoin alters Purkinje cell axon morphology and targeting in vitro. Knoth, R; Tauer, U; Volk, B, 1998)	1.74
" Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates."	( Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Birkett, DJ; Miners, JO, 1998)	0.3
"The clinical pharmacokinetic dosing service for phenytoin applied in this study contributed significantly to the success of epilepsy management."	( Benefits of a clinical pharmacokinetic service in optimising phenytoin use in the western Cape. Folb, PI; Kies, BM; Seymour, MA; Valodia, P, 1998)	0.8
" Anticonvulsant ED50s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 231 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) micromol/kg, compound 5 presenting with an ED50 value higher than 650 micromol/kg."	( Anticonvulsant activity and interactions with neuronal voltage-dependent sodium channel of analogues of ameltolide. Lambert, D; Masereel, B; Poupaert, JH; Stables, JP; Vamecq, J, 1998)	0.3
" The data indicate that kindling alters the dose-response of phenytoin in that a high anticonvulsant dose becomes ineffective or proconvulsant after kindling, possibly by an increased sensitivity of the kindled brain to proconvulsant effects of phenytoin which normally only occur at much higher doses."	( Limbic epileptogenesis alters the anticonvulsant efficacy of phenytoin in Sprague-Dawley rats. Cramer, S; Ebert, U; Löscher, W, 1998)	0.78
" Thus, the phenytoin dosing program has acceptable performances when at least 1 Css is known, and represents a potential tool to assist the clinician in the particular condition of outpatient population."	( Evaluation of a bayesian pharmacokinetic program for phenytoin concentration predictions in outpatient population. Boulieu, R; Fischer, C; Gaulier, JM, )	0.77
" During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight."	( Pediatric use of intravenous and intramuscular phenytoin: lessons learned. Wheless, JW, 1998)	0.78
" The assay was tested under in vivo conditions by administration of a pulse dose of the stable isotope analogue to a single rat dosed to steady-state with fosphenytoin, a phenytoin prodrug."	( A capillary GC-MS method for analysis of phenytoin and [13C3]-phenytoin from plasma obtained from pulse dose pharmacokinetic studies. Birnbaum, AK; Nelson, MH; Nyhus, PJ; Remmel, RP, 1998)	0.76
" Determination of the elimination half-life may provide a basis for selecting a dosing interval and predicting the time to steady-state concentration."	( Pharmacokinetics of antiepileptic drugs. Browne, TR, 1998)	0.3
" The plasma concentrations of DPH after intravenous dosing of EDPH declined in a biexponential manner, although two different elimination patterns were observed in these rats."	( Enhancement of the oral bioavailability of phenytoin by N-acetylation and absorptive characteristics. Iwaki, M; Kawaratani, D; Muraoka, O; Ogiso, T; Tanabe, G; Tanino, T, 1998)	0.56
" A further difference to the Wistar strain is the truncated dose-response with loss of anticonvulsant efficacy at 75 mg/kg in kindled Sprague-Dawley rats, which may, at least in part, explain the inconsistent results reported on the anticonvulsant efficacy of PHT in this strain in the literature."	( Selection of phenytoin responders and nonresponders in male and female amygdala-kindled Sprague-Dawley rats. Cramer, S; Ebert, U; Löscher, W, 1998)	0.67
" From our experience, careful and individual dosing of fosphenytoin in this age group can be considered."	( Fosphenytoin in infants. Caviness, VS; Krishnamoorthy, KS; Soman, TB; Takeoka, M, 1998)	1.17
" Group 1, intraperitoneal injection of phenytoin with a dosage of 50 mg/kg per day; Group 2, local use of phenytoin with a dosage of 40 mg/kg was injected in the fracture site every seventy-two hours, and Group 3, injection mormal saline of in the control group."	( [The effect of phenytoin in healing of fracture of rabbits]. Meng, Z; Yang, T; Yang, Z, 1997)	0.92
"6 micrograms/mL; the dosage of phenytoin was decreased and the symptoms later resolved."	( Ticlopidine-induced phenytoin toxicity. Klaassen, SL, 1998)	0.91
" Monitoring serum phenytoin levels during chronic therapy is an invaluable therapeutic aid, enabling dosage adjustments to be made in order to achieve a level within the therapeutic range."	( A study of the pharmacokinetics of phenytoin (diphenylhydantoin) in epileptic patients, and the development of a nomogram for making dose increments. Richens, A, 1975)	0.87
"05), and dose-response studies (10-50 KU/kg) at 8 h showed maximal respective 4-fold and 2-fold increases in maternal and embryonic activities with a 50 KU/kg dose (p < ."	( Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity. Wells, PG; Winn, LM, 1999)	0.54
" Phenytoin concentrations in hair sections correlated with the oral daily dosage of the drug."	( Determination of phenytoin in sections of head hair: a preliminary study to evaluate the history of drug use. Assithianakis, P; Helidonis, E; Michalodimitrakis, MN; Psillakis, T; Stefis, A; Tsatsakis, AM; Vlahonikolis, IG, 1998)	1.55
" Twelve adult patients with seizures controlled by an individualized fixed dosage of antiepilepsy medication (carbamazepine or phenytoin) participated in each study."	( Lack of pharmacokinetic drug interactions between tiagabine and carbamazepine or phenytoin. Boellner, SW; Cao, GX; Cato, A; Guenther, HJ; Gustavson, LE; Qian, JX; Sommerville, KW, 1998)	0.73
"Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines."	( Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. Chen, C; Cox, E; Fiedler-Kelly, J; Grasela, TH; Risner, ME; Womble, GP, 1999)	0.3
" This study sought to determine the lowest dosage of stiripentol (STP) protective against phenytoin-induced teratogenesis in a mouse model, and to determine mechanistically if inhibition of oxidative metabolism by STP in vitro decreased production of reactive phenytoin (PHT) metabolites."	( Effect of stiripentol dose on phenytoin-induced teratogenesis in a mouse model. Bajpai, M; Bennett, GD; Finnell, RH; Levy, RH; Mather, GG; Wlodarczyk, B, )	0.64
" Transfected cells were dosed with several known inducers of CYP3A4 and the levels of SPAP were measured."	( A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Gibson, GG; Goldfarb, PS; Gray, TJ; Ogg, MS; Tarbit, M; Williams, JM, 1999)	0.3
"With the initiation of FBM therapy in subjects receiving PHT, the PHT dosage should be reduced by 20%."	( Coadministration of phenytoin and felbamate: evidence of additional phenytoin dose-reduction requirements based on pharmacokinetics and tolerability with increasing doses of felbamate. Lyness, WH; Perhach, JL; Rosenberg, A; Sachdeo, R; Sachdeo, S; Shumaker, RC; Wagner, ML; Ward, D, 1999)	0.63
" However, it occurs most often in patients on polytherapy, usually after increasing dosage and with toxic serum levels."	( Dyskinesia induced by phenytoin. Cendes, F; Montenegro, MA; Scotoni, AE, 1999)	0.62
"To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy."	( Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures. Driscoll-Bannister, SM; Frazier, LM; Garnett, WR; O'Hara, KA; Pugh, CB; Rafi, JA, )	0.62
"It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study."	( Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures. Driscoll-Bannister, SM; Frazier, LM; Garnett, WR; O'Hara, KA; Pugh, CB; Rafi, JA, )	0.66
" On the other hand, for the elderly receiving phenytoin monotherapy, the initiation of phenytoin administration should occur at lower doses than would be customary for younger adults, and phenytoin blood concentrations should be appropriately monitored in order to evaluate individual Vmax and Km values for informed dosage adjustments."	( Differential kinetics of phenytoin in elderly patients. Bachmann, KA; Belloto, RJ, 1999)	0.87
" Valproate, when the proper therapeutic dosage was belatedly realized, was seen as a superior treatment for generalized and partial epilepsies."	( Clinical experience with new antiepileptic drugs: antiepileptic drugs in Europe. Loiseau, PJ, 1999)	0.3
" Because dosing is often modest, cost should rarely be the overriding factor in choosing a drug for a patient with newly diagnosed epilepsy in the developed world."	( Monostars: an aid to choosing an antiepileptic drug as monotherapy. Brodie, MJ, 1999)	0.3
" The gabapentin dosage was titrated to effective tolerated dose up to 2400 mg/day."	( Gabapentin as adjunctive therapy for partial seizures. Bruni, J, 1999)	0.3
" Subsequent determination of individual-specific DPH maintenance dosage and volume of distribution data suitable for use in routine therapeutic concentration management procedures."	( Practical management of therapeutic diphenylhydantoin concentrations in children. Parkin, DP; Schoeman, JF; Seifart, HI; Smit, A, 1999)	0.3
"In all subjects evaluated epilepsy was unsatisfactorily controlled because of inadequate DPH dosage regimens."	( Practical management of therapeutic diphenylhydantoin concentrations in children. Parkin, DP; Schoeman, JF; Seifart, HI; Smit, A, 1999)	0.3
" Dosage adjustments were made in 47."	( Optimization of phenytoin therapy in adults with epilepsy in the Western Cape, South Africa. Folb, PI; Kies, BM; Seymour, MA; Valodia, PN, 1999)	0.65
"The objective of this randomized, double-blind, two-period crossover study was to investigate whether concomitant steady-state lansoprazole influences the pharmacokinetics of CYP2C9 substrates using single intravenously dosed phenytoin as a model substrate."	( Lack of pharmacokinetic interaction between lansoprazole and intravenously administered phenytoin. Cavanaugh, JH; Karol, MD; Locke, CS, 1999)	0.71
" Two steady-state dosing rate and serum phenytoin minimum concentration (Cmin) pairs were obtained for each patient administered oral phenytoin alone, then phenytoin plus 250 mg ticlopidine twice daily."	( Ticlopidine inhibits phenytoin clearance. Abernethy, DR; Donahue, S; Flockhart, DA, 1999)	0.89
" After lamotrigine was added for better seizure control and the dosage of gabapentin was tapered, anorgasmia improved."	( Improved sexual function in three men taking lamotrigine for epilepsy. Carwile, ST; Husain, AM; Miller, PP; Radtke, RA, 2000)	0.31
" They were taking PHT in a dosage ranging from 100 to 300 mg daily, in mono or polytherapy regimen, during 1-5 previous years."	( Phenytoin as the first option in female epileptic patients? da Silva, VR; Molinari, MA; Trevisol-Bittencourt, PC; Troiano, AR, 1999)	1.75
" The aim of the present study was to investigate the correlation between the dosage and duration of treatment with phenytoin and the occurrence of cerebellar atrophy."	( [Dose-dependent relationship of chronic use of phenytoin and cerebellar atrophy in patients with epilepsy]. Cendes, F; Dantas, CD; Del Negro, A; Montenegro, MA; Zanardi, V, 2000)	0.77
" The authors conclude that the addition of levetiracetam did not bring about clinically important changes in phenytoin pharmacokinetic parameters and that it is not necessary to change the phenytoin dosing rate when levetiracetam is added to phenytoin."	( Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined by new technique. Baltes, E; Browne, TR; Jensen, CM; Josephs, E; Leppik, IE; Paz, J; Szabo, GK, 2000)	0.76
"To systematically review the reported interaction between oral dosage forms of phenytoin and enteral feeding formulations with respect to the evidence supporting or refuting its existence, proposed mechanism(s) underlying the interaction, and recommended interventions."	( Phenytoin and enteral feedings: does evidence support an interaction? Au Yeung, SC; Ensom, MH, )	1.8
" Clinicians should be aware of this potential drug-nutrient interaction and design a patient-specific care plan that includes consideration of the enteral feeding formulation and method of administration, as well as the phenytoin dosage form, schedule of administration, and monitoring."	( Phenytoin and enteral feedings: does evidence support an interaction? Au Yeung, SC; Ensom, MH, )	1.76
" We have reported previously that 7-day dosing with DEHP induced a higher bromodeoxyuridine labeling index (LI) in binuclear octoploid (2x4N) rat hepatocytes than did DCB, suggesting that induction of DNA synthesis in 2x4N hepatocytes might represent a more substantial carcinogenic risk."	( The nongenotoxic hepatocarcinogens diethylhexylphthalate and methylclofenapate induce DNA synthesis preferentially in octoploid rat hepatocytes. Hasmall, SC; Roberts, RA, )	0.13
" The wide variation in dose-response and dose-toxicity relationships may reflect different neurobiologies causing refractory epilepsy and differential efficacy of AED combinations."	( Topiramate in refractory epilepsy: a prospective observational study. Brodie, MJ; Sills, GJ; Stephen, LJ, 2000)	0.31
" These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4."	( The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. Thyrum, PT; Wong, YW; Yeh, C, 2001)	0.61
"1 microg/mL when fluvoxamine was coadministered, although the daily dosage of phenytoin and other drugs had not changed."	( Phenytoin intoxication induced by fluvoxamine. Higuchi, S; Ieiri, I; Kojima, K; Mamiya, K; Ninomiya, H; Tashiro, N; Yukawa, E, 2001)	1.98
" Embryonic heart rate was also recorded on individual days after dosing days 9-16."	( Phenytoin-induced cleft palate: evidence for embryonic cardiac bradyarrhythmia due to inhibition of delayed rectifier K+ channels resulting in hypoxia-reoxygenation damage. Azarbayjani, F; Danielsson, BR, 2001)	1.75
" As the novel microphysiometer works under regular cell culture conditions, cells can be repeatedly simulated with drugs to complete dose-response curve within a few hours."	( A novel microphysiometer based on MLAPS for drugs screening. Ping, W; Qingtao, Z; Rong, L; Weimin, Y; Xiaoxiang, Z; Xuesong, Y; Yicong, W, 2001)	0.31
" Since phenytoin has a narrow therapeutic index and genotyping may be carried out rapidly and at low cost, dosage adjustment based on CYP2C9 genotype, especially at the induction of therapy, would be of value in order to lower the risk of concentration dependent drug intoxications in carriers."	( The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. de Haan, K; Steijns, LS; van der Weide, J; van Weelden, MJ, 2001)	1
" The cerebellar signs represented drug over dosage and toxicity and persisted long after omission of phenytoin."	( Cerebellar atrophy in an epileptic child: is it due to phenytoin? Ahuja, SR; Karande, S; Kulkarni, MV, )	0.59
" Rates of metabolism in children may be much faster than in nonelderly adults, requiring dosing adjustments to ensure enough medication is used to control seizures."	( Treatment of epilepsy in 3 specialized populations. Leppik, IE, 2001)	0.31
"The aims of the present study were (1) to investigate and quantify the pharmacokinetics, including inter-occasion variability and covariate relationships, of busulphan in BMT patients and (2) to develop a user-friendly initial dosing and therapeutic drug monitoring (TDM) strategy for the treatment of those patients with busulphan."	( Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients. Bekassy, A; Hassan, M; Hassan, Z; Jonsson, EN; Karlsson, MO; Ljungman, P; Nilsson, C; Oberg, G; Ringden, O; Sandström, M, 2001)	0.31
"We compared predicted phenytoin serum concentrations using three Michaelis-Menten pharmacokinetic dosing methods with actual concentrations obtained from physician dosing in an outpatient neurology practice."	( Three Michaelis-Menten pharmacokinetic dosing methods compared with physician dosing of phenytoin in an outpatient neurology practice. Akbari, S; Cobb, HH; Spruill, WJ; Wade, WE, 2001)	0.85
" The phenytoin dosage was decreased and the symptoms resolved."	( Phenytoin and fluorouracil interaction. Brodribb, TR; Gilbar, PJ, 2001)	2.27
" Choreoathetosis disappeared when the phenytoin dosage was decreased."	( Phenytoin-induced choreoathetosis in patients with severe myoclonic epilepsy in infancy. Awaya, Y; Hayashi, K; Oguni, H; Osawa, M; Saito, Y, 2001)	2.02
" The impact of a clinical pharmacist participating in the care of patients with head injury on posttraumatic seizure prophylaxis with regard to phenytoin dosing and monitoring, cost avoidance, and patient outcome, was measured retrospectively."	( Pharmacist impact on posttraumatic seizure prophylaxis in patients with head injury. Brophy, GM; Garnett, WR; Schrote, GL; Tesoro, EP, 2002)	0.52
" Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population."	( Influence of phenytoin on the disposition of irinotecan: a case report. Berg, S; Bernstein, M; Blaney, SM; Cherrick, I; Kuttesch, N; Murry, DJ; Salama, V, 2002)	0.68
"The purpose of this study was to investigate the relationship of changes in the enzyme-inducing anticonvulsant daily dosage (drug score) to variations in urinary D-glucaric acid excretion and gamma-glutamyltransferase and beta-glucuronidase serum activities."	( Relationship between changes in drug score, D-glucaric acid excretion, and gamma-glutamyltransferase and beta-glucuronidase serum activities during anticonvulsant treatment. Fernández, MP; Hermida, J; Tutor, JC, 2002)	0.31
" Awareness and application of this knowledge will improve drug use in clinical practice and provide the physician with further appreciation that standard drug dosing may not be appropriate in all patients."	( Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450-metabolized drugs. Bertino, JS; Nafziger, AN; Rogers, JF, 2002)	0.31
" It is essential to monitor the blood concentrations of sirolimus and adjust the sirolimus dosage when phenytoin administration begins or ends."	( Phenytoin decreases the blood concentrations of sirolimus in a liver transplant recipient: a case report. Fridell, JA; Fung, JJ; Jain, AK; Patel, K; Rao, KN; Venkataramanan, R; Virji, M, 2003)	1.98
" The population pharmacokinetics of phenytoin in children may provide a usefull index for individualization of dosage regimen."	( [Population pharmacokinetics of phenytoin in pediatric patients]. Liang, WQ; Wang, J; Wu, JJ, 2003)	0.88
" BSA would serve as a practical alternative to LW for scaling adult dosage of metabolically eliminated drugs to children."	( Developmental changes in the liver weight- and body weight-normalized clearance of theophylline, phenytoin and cyclosporine in children. Echizen, H; Kanamori, M; Takahashi, H, 2002)	0.53
"001), but not with age and mean daily dosage of phenytoin (P>0."	( Cerebellar volume and long-term use of phenytoin. Cendes, F; De Marcos, FA; Ghizoni, E; Kobayashi, E; Li, LM, 2003)	0.84
"3-fold after dosing TAT-59 and 500 microM fosphenytoin, respectively."	( Absorption rate limit considerations for oral phosphate prodrugs. Fleisher, D; Flynn, G; Forsberg, M; Heimbach, T; Leppänen, J; Li, LY; Matsunaga, Y; Oh, DM; Savolainen, J, 2003)	0.58
" At baseline (before VGB), serum PHT remained unaffected (85 +/- 30 micromol l(-1)) after switching PHT dosage to the intravenous route, indicating that the oral availability of the drug was virtually complete."	( Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability. Bartoli, A; Gatti, G; Marchiselli, R; Michelucci, R; Perucca, E; Pisani, F; Richens, A; Tassinari, CA; Timmings, P; Zaccara, G, 1993)	0.56
" Hill slope coefficients for the tested anticonvulsants indicate that the dose-response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide."	( Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats. Jevtovic-Todorovic, V; Rastogi, AJ; Todorovic, SM, 2003)	0.52
" Excessive drowsiness can be avoided by proper dosage and proper timing of drug administration."	( Treatment of epilepsy. BAILEY, AA, 1963)	0.24
" loading and the necessity to individualize phenytoin dosing after day 5 were demonstrated."	( Rapid i.v. loading with phenytoin with subsequent dose adaptation using non-steady-state serum levels and a Bayesian forecasting computer program to predict maintenance doses. Martinelli, EF; Mühlebach, SF, 2003)	0.89
" Additional supporting findings demonstrated that 43-71% of patients with partial onset, generalised or undetermined epilepsy were seizure free after oxcarbazepine monotherapy (mean dosage 27."	( Spotlight on oxcarbazepine in epilepsy. Bang, LM; Goa, KL, 2004)	0.32
" A dose-response relationship of phenytoin in this regard is expected and needs further investigations."	( Studying long-term effect of phenytoin either alone or combined with ascorbic acid on the anesthetic effect of urethane in rats. Abdulla, MM; El Desoky, ES, 2004)	0.9
" This clinical policy focuses on 6 critical questions: What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to a baseline normal neurologic status?Which new-onset seizure patients who have returned to a normal baseline require a head computed tomography (CT) scan in the emergency department (ED)?Which new-onset seizure patients who have returned to normal baseline need to be admitted to the hospital and/or started on an antiepileptic drug?What are effective phenytoin or fosphenytoin dosing strategies for preventing seizure recurrence in patients who present to the ED after having had a seizure with a subtherapeutic serum phenytoin level?What agent(s) should be administered to a patient in status epilepticus who continues to seize after having received benzodiazepine and phenytoin?When should electroencephalographic (EEG) testing be performed in the ED? Recommendations for patient management are provided for each 1 of these topics on the basis of strength of evidence (Level A, B, or C)."	( Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. , 2004)	0.48
" The starting dosage of phenytoin was 20 or 22 mg/kg body weight (BW) q12h, and the maintenance dosage varied from 8 to 17 mg/kg BW q12h."	( Phenytoin sodium as a treatment for ventricular dysrhythmia in horses. Ververs, FF; Wijnberg, ID, )	1.88
" Management should be individualized to each patient; dosage or medication adjustments may be necessary."	( Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. Bertz, RJ; Eron, JJ; Gaedigk, A; Kashuba, AD; Lim, ML; Min, SS; Robinson, M, 2004)	0.58
"To search for the optimal dosage of phenytoin in patients with epilepsy based on the metabolic activities of CYP2C9 and CYP2C19 polymorphisms, a total of 169 patients receiving phenytoin treatment for more than 1 month were recruited."	( Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Chang, CJ; Chen, CC; Hung, CC; Lin, CJ; Liou, HH, 2004)	0.9
"A 73-year-old Taiwanese woman with end-stage renal disease received oral codeine phosphate 30 mg 4 times daily for her back and rib pain without adjustment of her dosage regimen."	( Probable codeine phosphate-induced seizures. Kao, SM; Kuo, SC; Lin, YC; Yang, YH, 2004)	0.32
" It is imperative to adjust the codeine dosage regimen based on patients' renal function to avoid the potential toxicity with overdose."	( Probable codeine phosphate-induced seizures. Kao, SM; Kuo, SC; Lin, YC; Yang, YH, 2004)	0.32
" A biomathematical model for multiple dosage regimen calculations of nonlinear metabolic systems in steady-state and a working example with phenytoin are presented."	( Classical Michaelis-Menten and system theory approach to modeling metabolite formation kinetics. Popović, J, )	0.33
" Dosage was adjusted to maintain the therapeutic blood levels used in the treatment of epilepsy."	( Treatment of posttraumatic stress disorder with phenytoin: an open-label pilot study. Douglas Bremner, J; Heim, CM; Mletzko, T; Nemeroff, CB; Reed, L; Siddiq, S; Welter, S; Williams, C, 2004)	0.58
"Phenytoin (PHT) dosing regimens are often determined based on experience in those aged <65 years rather than in those aged >or=65 years."	( Phenytoin use in elderly nursing home residents. Birnbaum, AK; Bowers, SE; Conway, JM; Graves, NM; Hardie, NA; Lackner, TE; Leppik, IE, 2003)	3.2
"PHT dose-dependently increased the hypoxia staining (6- and 11-fold after maternal dosing of 100 and 150 mg/kg, respectively) during the period I(Kr) is expressed and functional (GD 10)."	( Phenytoin teratogenicity: hypoxia marker and effects on embryonic heart rhythm suggest an hERG-related mechanism. Azarbayjani, F; Blomgren, B; Danielsson, BR; Danielsson, C; Johansson, A; Sköld, AC, 2005)	1.77
"Steady-state F-PHT serum concentrations, PHT dosing history, and associated information were collected prospectively."	( Estimation of population pharmacokinetic parameters of free-phenytoin in adult epileptic patients. Aarons, L; Ahmed, IA; Deleu, D, )	0.37
"We report a series of 102 adult patients who received standardized high dosage intravenous valproate in various emergency situations, including status epilepticus."	( Intravenous valproate as an innovative therapy in seizure emergency situations including status epilepticus--experience in 102 adult patients. Peters, CN; Pohlmann-Eden, B, 2005)	0.33
" These results provide evidence of a drug target polymorphism associated with the clinical use of AEDs and set the stage for a prospective evaluation of how pharmacogenetic diagnostics can be used to improve dosing decisions in the use of phenytoin and carbamazepine."	( Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Cavalleri, GL; Depondt, C; Goldstein, DB; Sander, JW; Schorge, S; Sen, A; Shorvon, SD; Sisodiya, SM; Soranzo, N; Tate, SK; Thom, M; Wood, NW, 2005)	0.72
" We measured the plasma phenytoin concentrations at steady-state in 20 routinely treated Japanese patients, and evaluated the usefulness of genotyping the CYP2C subfamily in predicting plasma concentrations and determining the dosage regimens of phenytoin."	( Evaluation of phenytoin dosage regimens based on genotyping of CYP2C subfamily in routinely treated Japanese patients. Aiba, T; Hashimoto, Y; Hongou, K; Miyawaki, T; Taguchi, M; Takizawa, M; Yagi, S, 2005)	1
" Blood phenytoin levels were taken after 1 week, 3 weeks, and 6 weeks, and dosage was adjusted to achieve blood levels of 10 to 20 microg/mL, to a maximum dose of 4 capsules per day or a minimum dose of 2 capsules per day."	( Controlled double-blind trial of phenytoin vs. fluoxetine in major depressive disorder. Belmaker, RH; Bersudsky, Y; Nemets, B, 2005)	1.06
"Phenytoin toxicity may result from intentional overdose, dosage adjustments, drug interactions, or alterations in physiology."	( Phenytoin poisoning. Craig, S, 2005)	3.21
" Linear regression analysis of dose-response relationship between the doses of 2-PMPA and their corresponding threshold values allowed the calculation of threshold increasing dose by 20% (TID20), which was 109."	( 2-phosphonomethyl-pentanedioic acid (glutamate carboxypeptidase II inhibitor) increases threshold for electroconvulsions and enhances the antiseizure action of valproate against maximal electroshock-induced seizures in mice. Czuczwar, SJ; Luszczki, JJ; Mohamed, M, 2006)	0.33
"A physician orders fosphenytoin to be administered intramuscularly in a dosage of 30 mL in volume."	( Administer single-site 30-mL intramuscular injection? Harrington, L, 2005)	0.64
" Clinical heterogeneity was assessed by reviewing differences across trials in characteristics of randomized patients, dosing protocols and trial design."	( Oxcarbazepine versus phenytoin monotherapy for epilepsy. Marson, AG; Muller, M; Williamson, PR, 2006)	0.65
" This combination of factors means that small increases in dosage can all too quickly result in high plasma levels and toxic symptoms."	( A case of phenytoin toxicity in a patient with advanced lung cancer. Jenkins, A, 2006)	0.74
"Phenytoin dosing is critical in cancer patients as to decreased absorption secondary to chemotherapy-induced gastrointestinal toxicity, increased phenytoin metabolism in the liver secondary to chemotherapy, extreme patient profile that falls outside the predicted pharmacokinetic population, frequent hypoalbuminaemia and polydrug treatment."	( Interactions of serum albumin, valproic acid and carbamazepine with the pharmacokinetics of phenytoin in cancer patients. Beijnen, JH; Boogerd, W; Huitema, AD; Joerger, M; Schellens, JH; van der Sande, JJ, 2006)	2
"The objective of this study was to compare the efficacy and safety of a chronotherapeutic dosing schedule of phenytoin and carbamazepine versus a conventional dosing schedule for the treatment of tonic-clonic epileptic patients."	( Chronotherapeutic dose schedule of phenytoin and carbamazepine in epileptic patients. Mahesh, SD; Sangle, S; Yegnanarayan, R, 2006)	0.82
" This has implications for dosing regimens relying on plasma phenytoin levels."	( Free phenytoin concentration measurement in brain extracellular fluid: a pilot study. Belli, A; Kitchen, N; Patsalos, P; Petzold, A; Ratnaraj, N; Russo, S; Sen, J; Smith, M; Tisdall, M, 2006)	1.09
"The aim of this study was to test the effect of supranutritional dosage of the natural antioxidant vitamin E (VitE) on phenytoin (PHT) induced developmental toxicity and possible long-term effects in rat offspring."	( Vitamin E supplementation in phenytoin induced developmental toxicity in rats: postnatal study. Dubovický, M; Kovacovský, P; Mach, M; Navarová, J; Ujházy, E, 2006)	0.83
" Switching from enteral to intravenous routes may require a dosage adjustment."	( Application of routine monitoring data for determination of the population pharmacokinetics and enteral bioavailability of phenytoin in neonates and infants with seizures. Al Za'abi, M; Charles, B; Donovan, T; Lanner, A; Xiaonian, X, 2006)	0.54
" Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients."	( Therapeutic monitoring of antiepileptic drugs for epilepsy. Dahl, ML; Kimland, E; Tomson, T, 2007)	0.34
" In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments."	( Therapeutic monitoring of antiepileptic drugs for epilepsy. Dahl, ML; Kimland, E; Tomson, T, 2007)	0.34
" The data suggest that chronic MK-801 treatment adversely affects the acquisition of IRA and AVD task performance and that the inclusion of phenytoin in the MK-801 dosing regimen blocks some of the adverse effects of chronic MK-801 treatment on IRA task acquisition."	( Effect of chronic MK-801 and/or phenytoin on the acquisition of complex behaviors in rats. Allen, RR; Hammond, TG; Paule, MG; Pearson, EC; Popke, EJ; Wright, LK, )	0.62
"To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used."	( Clinical utility of a continuous intravenous infusion of valproic acid in pediatric patients. Baumann, RJ; Cook, AM; Farzam, F; Kuhn, RJ; Lewis, DA; Taylor, LM, 2007)	0.34
" Further investigations with an approach to dose assessment that includes comprehensive interpretation of both pharmacogenetic and pharmacokinetic data along with understanding of the mechanism of drug interactions in dosage adjustment is warranted."	( Contributions of CYP2C9/CYP2C19 genotypes and drug interaction to the phenytoin treatment in the Korean epileptic patients in the clinical setting. Kim, JW; Lee, ST; Lee, SY, 2007)	0.57
" Instead, single dosing on specific days is proposed to be a better way to characterize the teratogenic potential of Ikr blocking drugs."	( Embryonic cardiac arrhythmia and generation of reactive oxygen species: common teratogenic mechanism for IKr blocking drugs. Danielsson, BR; Danielsson, C; Nilsson, MF, 2007)	0.34
"The purpose of the study was to demonstrate how the interaction between phenytoin and tacrolimus (FK 506) can be managed clinically and to characterize the change in FK 506 levels after discontinuation of phenytoin in two Japanese heart transplant recipients with different dosing periods ofphenytoin."	( Drug interactions between tacrolimus and phenytoin in Japanese heart transplant recipients: 2 case reports. Hanatani, A; Kotake, T; Morishita, H; Nakatani, T; Ochi, H; Takada, M; Ueda, T; Wada, K, 2007)	0.84
"The persistence of CYP induction after discontinuing phenytoin is dependent on the history of administration and, perhaps, on the dosing period in particular."	( Drug interactions between tacrolimus and phenytoin in Japanese heart transplant recipients: 2 case reports. Hanatani, A; Kotake, T; Morishita, H; Nakatani, T; Ochi, H; Takada, M; Ueda, T; Wada, K, 2007)	0.86
"On the basis of epileptic model induced by pentylenetetrazol (PTZ), cognitive impairment model was induced by kindling epilepsy with PTZ everyday, which were then di-vided into the model-1 group, the CZD-1 group, the nimodipine-1 group, and those by injecting large dosage phenytoin sodium were divided into the model-2 group, the CZD-2 group and the nimodipine-2 group."	( [Influence of repeated seizures and large dosage anti-epileptic drug on phosphorylated cAMP response element binding protein in rat's hippocampus and effect of Caoguo Zhimu Decoction]. He, J; Ma, SL, 2007)	0.52
"The authors report an Indian adult female patient with a history of generalized tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity on therapeutic dosage of this antiepileptic drug."	( Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Chandrasekaran, A; Chanolean, S; Narayan, SK; Ramasamy, K, )	0.79
" We report a child presenting with ileus, hypothermia and lethargy after receiving supratherapeutic dosing of phenytoin after a concentration miscalculation."	( Unusual presentation of iatrogenic phenytoin toxicity in a newborn. DeGreeff, J; Lowry, JA; Scalzo, AJ; Vandover, JC, 2005)	0.82
" Physicians must be aware of inaccuracies in reference manuals that may result in dosing errors."	( Unusual presentation of iatrogenic phenytoin toxicity in a newborn. DeGreeff, J; Lowry, JA; Scalzo, AJ; Vandover, JC, 2005)	0.61
" In such patients, alternative methods such as HPLC should be used to prevent dosage errors."	( Undetectable phenytoin serum levels by an automated particle-enhanced turbidimetric inhibition immunoassay in a patient with monoclonal IgM lambda. Brauchli, YB; Krähenbühl, S; Scholer, A; Schwietert, M, 2008)	0.72
" This raises concerns relating to the dosage and monitoring of phenytoin in these patients compared with its routine use in epileptic patients."	( Dosing and therapeutic monitoring of phenytoin in young adults after neurotrauma: are current practices relevant? Chetty, M; Frend, V, )	0.64
" Reduced PHT dosage requirements may be due to age-related changes in patients' sensitivity to the therapeutic and toxic effects of the drug."	( Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy. Ahn, JE; Birnbaum, AK; Brundage, RC; Cloyd, JC; Conway, JM; Leppik, IE; Marino, SE; Musib, LC; Ramsay, RE; Rarick, JO; White, JR, 2008)	1.79
" From a practical point of view, for the subpopulation of burn patients who eliminate drugs extremely rapidly, higher doses and/or shorter dosing intervals are required to avoid treatment inefficacy."	( Influence of burns on pharmacokinetics and pharmacodynamics of drugs used in the care of burn patients. Blanchet, B; Jullien, V; Tod, M; Vinsonneau, C, 2008)	0.35
" Case reports describe phenytoin toxicity secondary to inappropriate dosage adjustments based solely on total serum concentrations in patients with hypoalbuminemia."	( Therapeutic drug monitoring of phenytoin in critically ill patients. Spriet, I; von Winckelmann, SL; Willems, L, 2008)	0.94
"This case reveals the clinical significance of genetic polymorphisms and the effect on phenytoin dosage requirements."	( Phenytoin toxicity due to genetic polymorphism. Bullock, MR; McCluggage, LK; Voils, SA, 2009)	2.02
" A Phenytoin overdose could be contributed to both inadequate dosing and missed repeated drug monitoring."	( Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion. Eyer, F; Felgenhauer, N; Pfab, R; Thürmel, K; Zilker, T, 2008)	1.25
" Its narrow therapeutic range enforces strictly adequate dosing and subsequent repeated drug monitoring of phenytoin."	( Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion. Eyer, F; Felgenhauer, N; Pfab, R; Thürmel, K; Zilker, T, 2008)	0.84
" For each class, the dosing scheme and practical issues related to administration are described, based on evidence when available in the literature."	( [Drugs for status epilepticus treatment]. Mazoit, JX; Navarro, V, 2009)	0.35
" An appropriate dosage of H(2)O(2) could hinder the occurrence of the direct photolysis."	( Degradation of selected pharmaceuticals in aqueous solution with UV and UV/H(2)O(2). Hu, C; Hu, X; Qu, J; Yang, M; Yuan, F, 2009)	0.35
"5 to 5 g/L) have been recommended, but few reports describe dose-response testing, the time to loss of consciousness, or the reliability of euthanasia."	( Evaluation and refinement of euthanasia methods for Xenopus laevis. Green, SL; McClure, DE; Torreilles, SL, 2009)	0.35
" The use of systemic corticosteroids in the treatment of TEN is controversial because of a lack of randomized, controlled, prospective studies, and because the effects of steroid therapy vary depending on the dosage and time of its administration during the course of TEN."	( Skin biopsies to assess response to systemic corticosteroid therapy in early-stage TEN: case report and review of the literature. Céspedes, YP; Nigra, TP; O'Donoghue, JM; Rockley, PF, 2009)	0.35
" TDM requests, interpretation and dosage adjustment recommendations were mainly responsible by residents."	( Effect of pharmacist participation in the health care team on therapeutic drug monitoring utilization for antiepileptic drugs. Faroongsarng, D; Kaewpibal, P; Ratanajamit, C; Setthawacharavanich, S, 2009)	0.35
"Although there appears to be more evidence for the use of lidocaine than phenytoin as adjunctive treatment for TCA-associated cardiotoxicity, specific clinical indications and dosing recommendations remain to be defined."	( What is the role of lidocaine or phenytoin in tricyclic antidepressant-induced cardiotoxicity? Benowitz, N; Foianini, A; Joseph Wiegand, T, 2010)	0.87
" When adjusting for age, sex, type of seizure, type of glioma, and dosage using univariate and multivariate models, there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values>0."	( Seizures in patients with glioma treated with phenytoin and levetiracetam. Anderson, SK; Lachance, DH; Merrell, RT; Meyer, FB, 2010)	0.62
" Bu dosing and continued until 24 hours after the last dose."	( Influence on Busilvex pharmacokinetics of clonazepam compared to previous phenytoin historical data. Bacigalupo, A; Buzyn, A; Cahn, JY; Carreras, E; Kröger, N; Puozzo, C; Sanz, G; Vernant, JP, 2010)	0.59
" Dosing and plasma levels of levetiracetam and concomitant antiepileptic drugs were reviewed retrospectively."	( Age and comedications influence levetiracetam pharmacokinetics in children. Dahlin, MG; Ohman, I; Wide, K, 2010)	0.36
" Therefore, the patient's daily dosage of oxcarbazepine and phenytoin were reduced."	( Phenytoin toxicity secondary to an oxcarbazepine-phenytoin 2C19 interaction. Kane, AJ; Soskin, DP; Stern, TA, )	1.82
" Equal volumes of three plasma samples corresponding to each time point of three discretely dosed rats with different compounds were pooled (cassette analysis)."	( High-throughput analysis of standardized pharmacokinetic studies in the rat using sample pooling and UPLC-MS/MS. Betnér, I; Briem, S; Bueters, T; Dahlström, J; Kvalvågnaes, K, 2011)	0.37
" With a total processing time for this assay of less than 3 hours, prediction of the optimal phenytoin dosage based on the CYP2C9 and CYP2C19 genotypes will be possible before commencement of therapy, resulting in the prevention of phenytoin overdoses in pediatric patients with epilepsy."	( [Development of rapid genotyping methods for single nucleotide polymorphisms of cytochrome P450 2C9 (CYP2C9) and cytochrome P450 2C19 (CYP2C19) and their clinical application in pediatric patients with epilepsy]. Ikumi, Y; Kagawa, Y; Mishima, N; Nishimura, S; Takahashi, Y; Yamamoto, Y, 2011)	0.59
" During the 3 months preceding admission, phenytoin dosing was stable and consecutive therapeutic concentrations were documented."	( Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient. Brandon Bookstaver, P; Miller, AD, 2011)	0.87
" This case suggests that when capecitabine and PHT are coadministered, PHT levels should be monitored frequently, and that PHT dosage should be adjusted accordingly if it cannot be replaced by an alternative anticonvulsant."	( [A case of toxicity caused by drug interaction between capecitabine and phenytoin in patient with colorectal cancer]. Fukui, E; Kawahara, K; Sakurai, M; Ueda, R; Yamada, R, 2011)	0.6
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."	( FDA-approved drug labeling for the study of drug-induced liver injury. Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)	0.37
" Serial pharmacokinetic sampling of atorvastatin was conducted on day 7 of atorvastatin dosing and day 70 of lamotrigine + atorvastatin dosing or day 28 of phenytoin + atorvastatin dosing."	( Effects of lamotrigine and phenytoin on the pharmacokinetics of atorvastatin in healthy volunteers. Alexander, S; Bullman, J; Fleck, R; Messenheimer, J; Miller, J; Nicholls, A; Van Landingham, K; Vuong, A, 2011)	0.86
" An in vivo study, verapamil (25mg/kg, per oral) was administered 2h before phenytoin (30mg/kg, per oral) dosing in male Wistar rats."	( Study on in situ and in vivo absorption kinetics of phenytoin by modulating P-glycoprotein with verapamil in rats. Bedada, SK; Ganji, D; Neerati, P, 2011)	0.85
" We found by combining both acupuncture and PHT with Selective Drug Uptake Enhancement by stimulating middle finger at the first segment of ventral (palmar) and lateral surfaces, as well as prescribing PHT with the dosage predetermined for each patient by Bi-Digital O-Ring Test (BDORT), the treatment outcome was much better resulted with less recurrence and intensity of pain during episodes of attack."	( Phenytoin (Dilantin) and acupuncture therapy in the treatment of intractable oral and facial pain. Lu, DP; Lu, GP; Lu, WI, 2011)	1.81
" The obtained equations in the present study could be applied for adjusting the dosage regimen and monitoring by using salivary phenytoin level in clinical practice."	( Correlation between serum and salivary phenytoin concentrations in Thai epileptic children. Jaiweerawattana, U; Liamsuwan, S, 2011)	0.84
" Because of the increasing worldwide incidence of obesity, there is a need for more information regarding the optimal dosing of drug therapy to be made available to prescribers."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
" Prediction of the effects of obesity on drug clearance, normalized by various body size scalars, is of potential value in the design of clinical studies during drug development and in the introduction of dosage adjustments that are likely to be needed in clinical practice."	( Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. Aarabi, M; Allabi, AC; Almond, LM; Ghobadi, C; Jamei, M; Johnson, TN; Rostami-Hodjegan, A; Rowland-Yeo, K, 2011)	0.37
" The dosage was adjusted according to the level of pain control and side-effects."	( Use of single- and multi-drug regimens in the management of classic (idiopathic) trigeminal neuralgia: an 11-year experience at a single Sri Lankan institution. Ariyawardana, A; Pallegama, R; Ranasinghe, A; Sitheeque, M, 2012)	0.38
"Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose-response relationship of DPH."	( Dose-response effects of diphenylhydantoin on pregnant dams and embryo-fetal development in rats. Baek, HS; Kim, JC; Kim, SH; Lee, IC; Lim, JH; Moon, C; Park, SC; Shin, DH, 2012)	0.38
" In addition, there appeared to be a dose-response relationship between stroke risk and PHT prescriptions."	( Comparative stroke risk of antiepileptic drugs in patients with epilepsy. Hsieh, CY; Lai, EC; Lin, SJ; Yang, YH, 2013)	0.39
"The obtained results indicated the need to consider patients' body surface area and the catalytic activities of liver enzymes aspartate aminotransferase and alkaline phosphatase when dosing phenytoin."	( Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug. Chan, DW; Chan, E; Ho, PC; Kong, ST; Lee, FX; Tan, WW, 2013)	0.83
" Mean phenytoin dosage between groups was not statistically significant."	( Association of CYP2C9 polymorphisms with phenytoin toxicity in Indian patients. Bendkhale, SR; Gogtay, NJ; Taur, SR; Thakkar, AN; Thatte, UM, )	0.88
" Although clinicians are aware of the interaction with two widely used antituberculosis agents, rifampin and isoniazid, few reports have described the implications for managing phenytoin dosing in this situation."	( Phenytoin-rifampin drug interaction in a hypoalbuminemic, renal failure patient: a complex clinical case. Hurdle, AC; Twilla, JD; Van Berkel, MA, 2013)	2.03
"The present study was aimed to characterize the anticonvulsant effects of piperine in combination with well established antiepileptic drug (AED) phenytoin, in the mouse maximal electroshock (MES)-induced seizure model by using the type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs)."	( Combination therapy of piperine and phenytoin in maximal electroshock induced seizures in mice: isobolographic and biochemical analysis. Khanam, R; Pillai, KK; Saraogi, P; Vohora, D, 2013)	0.87
"To investigate PHT performance in reaching therapeutic target serum concentration rapidly and sustainably, a Bayesian forecasting (BF) regimen was compared to conventional dosing (CD), according to the official summary of product characteristics."	( Intravenous phenytoin: a retrospective analysis of Bayesian forecasting versus conventional dosing in patients. Mühlebach, S; Tobler, A, 2013)	0.77
" The conventional dosage was performed without written guidance."	( Intravenous phenytoin: a retrospective analysis of Bayesian forecasting versus conventional dosing in patients. Mühlebach, S; Tobler, A, 2013)	0.77
" As prolonged subtherapeutic nevirapine dosage leads to the emergence of resistance, single-dose nevirapine could be used with phenytoin as an alternative if other ARVs were unavailable."	( Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. Aitken, S; Burger, DM; Chunda, C; Fillekes, Q; Gibb, DM; Kankasa, C; Kisanga, ER; Muro, EP; Thomason, MJ; Walker, AS, 2013)	0.92
"2 mg/L during rewarming was observed and was not explained by dosing differences."	( Therapeutic hypothermia decreases phenytoin elimination in children with traumatic brain injury. Adelson, PD; Anderson, KB; Bell, MJ; Bies, RR; Empey, PE; Kochanek, PM; Poloyac, SM; Velez de Mendizabal, N, 2013)	0.67
" No prior studies have examined current dosing practices in an Australasian intensive care unit (ICU) setting."	( Phenytoin loading doses in adult critical care patients: does current practice achieve adequate drug levels? Hennig, S; Jarrett, P; Lipman, J; Martin, J; Putt, MT; Roberts, JA; Salmon, N; Udy, AA, 2013)	1.83
" The dosage regimen should be adjusted accordingly to gain a better clinical outcome."	( Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients. Panomvana, D; Towanabut, S; Traiyawong, T, 2013)	0.6
" A loading dose of intravenous phenytoin 2700 mg was administered, followed by maintenance dosing of intravenous phenytoin 150 mg every 8 hours."	( Phenytoin removal by continuous venovenous hemofiltration. Herrmann, DJ; Oltrogge, KM; Peppard, WJ; Regner, KR; Saleh, M, 2013)	2.12
" Colesevelam (3750mg once daily) was dosed throughout the pharmacokinetic sampling period."	( Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. He, L; Lee, J; Mendell-Harary, J; Tao, B; Walker, J; Wickremasingha, P; Wight, D, 2014)	0.62
" In this study, we report the electrical detection of phenytoin as an antiepileptic medication with a narrow therapeutic dosage range to which therapeutic drug monitoring (TDM) is applied."	( Detection of the antiepileptic drug phenytoin using a single free-standing piezoresistive microcantilever for therapeutic drug monitoring. Chang, KF; Huang, LS; Lai, DM; Lin, LY; Pheanpanitporn, Y; Yen, YK, 2014)	0.93
" Current dabigatran dosing guidelines use the Cockcroft-Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys)."	( Correlation between trough plasma dabigatran concentrations and estimates of glomerular filtration rate based on creatinine and cystatin C. Barclay, ML; Begg, EJ; Chin, PK; Jensen, BP; Patterson, DM; Roberts, RL; Wallace, MC; Wright, DF; Zhang, M, 2014)	0.4
" The purpose of this guideline is to provide information for the interpretation of HLA-B and/or CYP2C9 genotype tests so that the results can guide dosing and/or use of phenytoin."	( Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Callaghan, JT; Caudle, KE; Klein, TE; Lee, MT; Mintzer, S; Rettie, AE; Smith, LH; Whirl-Carrillo, M, 2014)	0.81
" Secondary end points were presence of early seizures (0 to 7 days post-TBI) or late seizures (8 days post-TBI to phone interview), use of anticonvulsant medication when interviewed, medication-related hospital complications, and a summary of phenytoin (PHT) and LEV dosing regimens."	( Long-term comparison of GOS-E scores in patients treated with phenytoin or levetiracetam for posttraumatic seizure prophylaxis after traumatic brain injury. Gabriel, WM; Rowe, AS, 2014)	0.82
"Pre-clinical trial of abbreviated LEV dosing in an experimental model of TBI Methods: After either controlled cortical impact (CCI) injury or sham surgery, rats received three 50 mg kg(-1) doses over 24 hours or vehicle."	( Abbreviated levetiracetam treatment effects on behavioural and histological outcomes after experimental TBI. Fowler, L; Hurwitz, M; Wagner, AK; Zou, H, 2015)	0.42
" These findings may guide (1) future experimental studies assessing minimal effective dosing for neuroprotection and anti-epileptogenesis and (2) treatment guideline updates for seizure prophylaxis post-TBI."	( Abbreviated levetiracetam treatment effects on behavioural and histological outcomes after experimental TBI. Fowler, L; Hurwitz, M; Wagner, AK; Zou, H, 2015)	0.42
"No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program."	( Impact of a phenytoin loading dose program in the emergency department. Brancaccio, A; Delgado, G; Giuliano, C; McNorton, K, 2014)	1.05
" The recovery of basal Pgp expression could allow the design of dosing schedules that optimize anticonvulsant therapy."	( Chronic administration of phenytoin induces efflux transporter overexpression in rats. Alvariza, S; Fagiolino, P; Feria-Romero, I; Orozco-Suárez, S; Vázquez, M, 2014)	0.7
" We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
" Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
"Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation."	( Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Buchsbaum, R; Chen, B; Choi, H; Detyniecki, K; Hirsch, LJ; Javed, A; Kato, K; Legge, A; Moeller, J, 2015)	0.42
" Dose-response curves for phenytoin and levetiracetam were generated in the three strains at 32 and 44 mA current intensities using both devices."	( Genetic background of mice strongly influences treatment resistance in the 6 Hz seizure model. Kaminski, RM; Leclercq, K, 2015)	0.72
" Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice."	( Treatment of cardiac arrhythmias in a mouse model of Rett syndrome with Na+-channel-blocking antiepileptic drugs. Glaze, DG; Herrera, JA; Kaufmann, WE; Neul, JL; Percy, AK; Pitcher, MR; Skinner, S; Ward, CS; Wehrens, XH, 2015)	0.62
"This study demonstrates that characterization of pharmacokinetics in a small number of dogs is useful in determining dosage regimens designed to attain targeted concentrations in clinical trials."	( Use of IV fosphenytoin pharmacokinetics to determine the loading dose for a clinical trial of canine status epilepticus. Cloyd, JC; Coles, LD; Leppik, IE; Mishra, U; Patterson, EE; Rivers, Z, 2015)	0.79
" The dose-response to DHA was obtained 15 min after intracerebroventricular (i."	( Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models. Babapour, V; Gavzan, H; Sardari, S; Sayyah, M, 2015)	0.42
"Phenytoin, a widely prescribed old-generation antiepileptic drug, requires careful individualization of dosage to compensate for its prominent pharmacokinetic variability."	( CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Franco, V; Perucca, E, 2015)	2.16
" The dose regimen of lidocaine varied, with some using bolus dosing alone; others used a combination of bolus and infusion therapy."	( Lidocaine for Status Epilepticus in Pediatrics. Gillman, LM; Kazina, CJ; Teitelbaum, J; West, M; Zeiler, FA; Zeiler, KJ, 2015)	0.42
" Future studies are needed to look at the dosing and monitoring of phenytoin and/or alternative anti-seizure prophylaxis in patients with traumatic brain injury."	( Anti-seizure prophylaxis in critically ill patients with traumatic brain injury in an intensive care unit. Chapman, MJ; Edwards, S; Milne, D; Shakib, S; Sundararajan, K, 2015)	0.65
" A nasogastric tube was immediately placed and the patient received treatment with a chelating agent dimercaptosuccinic acid (DMSA)/succimer 800 mg orally three times a day, a dosage decided on the basis of her body weight, plus phenytoin 125 mg intravenously three times a day."	( Elemental mercury mixed with alcohol injected intravenously as a suicide attempt. Karatapanis, S; Kotis, A; Lamprianou, F; Ntetskas, G, 2015)	0.6
" In a prior long-term investigation, we showed the excellent performance of pharmacy-assisted Bayesian forecasting support for optimal dosing in hospitalized patients treated with phenytoin."	( Free phenytoin assessment in patients: measured versus calculated blood serum levels. Hösli, R; Huber, A; Mühlebach, S; Tobler, A, 2016)	1.14
" Factors contributing to bias and imprecision include the following: albumin concentration, free phenytoin assay temperature, experimental conditions (eg, timing of concentration sampling, steady-state dosing conditions), renal function, age, concomitant medications, and patient type."	( A Comprehensive Review on the Predictive Performance of the Sheiner-Tozer and Derivative Equations for the Correction of Phenytoin Concentrations. Ensom, MH; Kiang, TK, 2016)	0.86
" This population PK model can be applied for optimizing topiramate dosage regimens in actual clinical practice."	( Factors influencing topiramate clearance in adult patients with epilepsy: A population pharmacokinetic analysis. Bae, EK; Jang, IJ; Kim, TJ; Lee, J; Lee, KJ; Lee, SK; Moon, J; Shin, D; Shin, JW; Shin, YW, 2016)	0.43
" The present study aims to establish a population pharmacokinetic (PPK) model of oral phenytoin in patients with intracranial tumor during the early periods, the first week, of post-craniotomy to optimize phenytoin dosage regimen."	( Population Pharmacokinetics of Phenytoin Based on NONMEM in Patients with Intracranial Tumor During the First Week of Post-Craniotomy. Huang, YA; Lei, Z; Li, L; Li, ZD; Liu, M; Wan, JH, 2016)	0.94
"Sixty-two patients with intracranial tumor were genotyped for CYP2C9 and CYP2C19 by real time PCR (TaqMan probe), and subsequently their phenytoin dosage regimens were designed according to the results of previous literature."	( Population Pharmacokinetics of Phenytoin Based on NONMEM in Patients with Intracranial Tumor During the First Week of Post-Craniotomy. Huang, YA; Lei, Z; Li, L; Li, ZD; Liu, M; Wan, JH, 2016)	0.92
" Clinical individualized dosage regimens of additional 50 patients were designed by above PPK model."	( Population Pharmacokinetics of Phenytoin Based on NONMEM in Patients with Intracranial Tumor During the First Week of Post-Craniotomy. Huang, YA; Lei, Z; Li, L; Li, ZD; Liu, M; Wan, JH, 2016)	0.72
"The final PPK model of oral phenytoin may be helpful to design phenytoin individualized dosage regimen at the early stage of post-craniotomy when characteristics of patients meet these of subpopulation in the study."	( Population Pharmacokinetics of Phenytoin Based on NONMEM in Patients with Intracranial Tumor During the First Week of Post-Craniotomy. Huang, YA; Lei, Z; Li, L; Li, ZD; Liu, M; Wan, JH, 2016)	1.01
" To prevent phenytoin intoxication, phenytoin dosage must be adjusted."	( Pharmacokinetic model analysis of interaction between phenytoin and capecitabine. Fukui, E; Hori, S; Ikenishi, M; Kawahara, K; Matsuyama, K; Miki, A; Miyazaki, S; Nakatsuka, E; Ohtori, T; Sakurai, M; Satoh, H; Sawada, Y; Ueda, M; Ueda, R, 2016)	1.06
" This model and these parameters allow us to predict the appropriate phenytoin dosage schedule when capecitabine is administered concomitantly."	( Pharmacokinetic model analysis of interaction between phenytoin and capecitabine. Fukui, E; Hori, S; Ikenishi, M; Kawahara, K; Matsuyama, K; Miki, A; Miyazaki, S; Nakatsuka, E; Ohtori, T; Sakurai, M; Satoh, H; Sawada, Y; Ueda, M; Ueda, R, 2016)	0.92
"This newly-developed model accurately describes changes in phenytoin concentration during concomitant capecitabine chemotherapy, and it may be clinically useful for predicting appropriate phenytoin dosage adjustments for maintaining serum phenytoin levels within the therapeutic range."	( Pharmacokinetic model analysis of interaction between phenytoin and capecitabine. Fukui, E; Hori, S; Ikenishi, M; Kawahara, K; Matsuyama, K; Miki, A; Miyazaki, S; Nakatsuka, E; Ohtori, T; Sakurai, M; Satoh, H; Sawada, Y; Ueda, M; Ueda, R, 2016)	0.93
"The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT)."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
" Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
"Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
"Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents."	( Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. Bastin, ML; Cook, AM; Oyler, DR; Smetana, KS, 2016)	0.43
" A population pharmacokinetic (PPK) analysis was performed to improve the topiramate dosage adjustment for individualized treatment."	( Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data. Ikeda, A; Ito, S; Matsubara, K; Sugimoto, M; Takeuchi, M; Yamamoto, S; Yano, I; Yonezawa, A, 2017)	0.46
" Simulations based on the final model showed that dosage adjustments allometrically scaling to body weight can equalize the serum concentrations in children of various ages and adults."	( Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data. Ikeda, A; Ito, S; Matsubara, K; Sugimoto, M; Takeuchi, M; Yamamoto, S; Yano, I; Yonezawa, A, 2017)	0.46
" Dosage adjustments based on body weight and concomitant antiepileptic drug help obtain the dosage of topiramate necessary to reach an effective concentration in each individual."	( Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data. Ikeda, A; Ito, S; Matsubara, K; Sugimoto, M; Takeuchi, M; Yamamoto, S; Yano, I; Yonezawa, A, 2017)	0.46
" We sought to determine whether there were regions in the dosage range of commonly used AEDs that were associated with superior efficacy in patients with refractory epilepsy."	( Association between antiepileptic drug dose and long-term response in patients with refractory epilepsy. Castagna, CE; Miller, AB; Poolos, NP; Story, TJ; Williams, S, 2017)	0.46
" Various clinical and demographic parameters were analysed, including comorbidities, drug history, seizure aetiology and type, incidence of hypotension/cardiac arrhythmia and the dosing data (ie the total dose, concentration and FOS IV infusion rate)."	( Incidence and risk factors of hypotension after intravenous fosphenytoin administration. Hwang, IG; Kim, DW; Kim, HK; Koh, IS, 2017)	0.69
" Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication."	( The efficacy of different kinds of intravenously applied antiepileptic drugs in the treatment of status epilepticus. How can it be determined? Redecker, J; Rösche, J; Wittstock, M, 2017)	0.46
" The patient continued to have seizure activity on continuous electroencephalography for which fosphenytoin dosing was increased with subsequent seizure control."	( Fosphenytoin-induced purple glove syndrome: A case report. Blunck, JR; Croom, JE; Fields, RK; Newman, JW, 2017)	1.29
" For UV/chlorination, the effect of FAC dosage and pH on the degradation of DPH was evaluated."	( Degradation of 5,5-diphenylhydantoin by chlorination and UV/chlorination: kinetics, transformation by-products, and toxicity assessment. Mansor, NA; Tay, KS, 2017)	0.46
" Modifying dosing according to SIRS will improve the prediction accuracy of drug concentration based on TDM."	( [Evaluation of Pharmacotherapy on Emergency and Intensive Care Medicine: The Influence of Intensity and Duration of Invasion]. Imai, T, 2017)	0.46
" Future studies should prospectively verify these observations and characterize dose-response relationships."	( Fosphenytoin pre-medication for pediatric extra-operative electrical stimulation brain mapping. Arya, R; Aungaroon, G; Byars, AW; Greiner, HM; Holland, KD; Horn, PS; Mangano, FT; Zea Vera, A, 2018)	1.1
" The purpose of this review is to provide an up-to-date evidence summary of the incidence and outcomes of seizures following an SAH as well as the use of different AEDs post-SAH in order to evaluate the need for seizure prophylaxis, the choice of AEDs, and their dosing considerations in SAH patients."	( Seizures and Choice of Antiepileptic Drugs Following Subarachnoid Hemorrhage: A Review. Buxton, J; Mahmoud, SH, 2017)	0.46
" Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug."	( Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries. Sasaki, E; Yokoi, T, 2018)	0.48
" We aimed to clarify the effects of genetic polymorphisms in both enzymes on daily PHT maintenance dosage in Asian epileptic patients by meta-analysis."	( The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis . Ai, CZ; Li, W; Liao, K; Liu, Y; Yu, X, 2018)	0.73
" Patients with heterozygous CYP2C9 or both heterozygous CYP2C9 and CYP2C19 showed a trend but not a statistically-significant decrease of PHT dose, but dosage adjustment was recommended."	( The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis . Ai, CZ; Li, W; Liao, K; Liu, Y; Yu, X, 2018)	0.73
"The meta-analysis indicates that CYP2C9 and CYP2C19 polymorphisms are associated with lower PHT maintenance dosage in Asian epileptic patients."	( The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis . Ai, CZ; Li, W; Liao, K; Liu, Y; Yu, X, 2018)	0.73
"Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used."	( Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Battino, D; Bonizzoni, E; Craig, J; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Tomson, T; Vajda, F, 2018)	0.48
"In the therapeutic drug monitoring group, clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control."	( AntiEpileptic drug Monitoring in PREgnancy (EMPiRE): a double-blind randomised trial on effectiveness and acceptability of monitoring strategies. Bagary, M; Coleman, J; D'Amico, M; Denny, E; Dodds, J; Eldridge, S; Greenhill, L; Hard, K; Kelso, A; Khan, KS; Marlin, N; McCorry, D; Middleton, L; Moss, N; Newton, S; Pirie, A; Pullen, A; Rikunenko, R; Roberts, T; Rogozińska, E; Thangaratinam, S; Weckesser, A, 2018)	0.48
" Simulation was performed to determine optimal loading dose and maintenance dosing regimens."	( Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population. Erklauer, J; Galati, M; Moffett, BS; Riviello, JJ; Schmees, LR; Weingarten, MM, 2018)	1.1
" Such a 'large N' NIR-based process analytical technology method can increase reliability of quality assessments in solid dosage manufacturing."	( A "Large-N" Content Uniformity Process Analytical Technology (PAT) Method for Phenytoin Sodium Tablets. Bandi, CK; Drazer, G; Drennen, JK; Friedman, R; Muzzio, FJ; Pawar, P; Reddy, D; Sowrirajan, K; Talwar, S; Wu, H, 2019)	0.74
"We evaluated DDIs and adjusted the dosage of drugs by monitoring the serum drug level."	( Drug-drug interactions among drugs prescribed for nontuberculous mycobacterial infection and epilepsy: A case report. Hatanaka, M; Ikeda, R; Matsumoto, N; Oda, Y; Sonoda, J; Tazaki, T; Yoshikawa, N, 2019)	0.51
" The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients."	( A systematic review of phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets in China. Chen, L; Han, X; Li, C; Li, Z; Ma, G; Shan, M; Zhang, L, 2018)	0.79
" Simulation results showed that the dosing interval should be reduced to achieve optimal dosing in neonates and infants, and the optimal dose required increases with weight."	( Optimal Dosing Regimen of Phenytoin for Korean Epilepsy Patients: From Premature Babies to the Elderly. Chae, D; Guk, J; Kim, JH; Lee, SG; Park, K, 2019)	0.81
" The results of the present study do not support the use of this gel at this dosage for the treatment of wounds in Brook Trout."	( Effect of a Misoprostol/Phenytoin Gel on Experimentally Induced Wounds in Brook Trout-A Preliminary Study. Coutant, T; Lair, S; Vergneau-Grosset, C, 2019)	0.82
"The delivery of drug molecules and their localization into the skin is the main purpose of the topical dosage forms."	( The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration. Abd El-Gawad, AEH; Borg, T; Motawea, A; Motawea, M; Tarshoby, M, 2019)	0.83
" To provide guidance in drug dosage decisions, further studies are required to evaluate all factors that may potentially influence the pharmacokinetics of phenytoin."	( Estimation of Phenytoin Pharmacokinetic Parameters in Saudi Epileptic Patients. Alotaibi, M; Alqahtani, S; Alsultan, A; Alzaidi, T, 2019)	1.07
" Collectively, healthcare providers should take these factors in consideration for optimal valproic acid dosage regimen."	( Estimation of apparent clearance of valproic acid in adult Saudi patients. Alandas, N; Alqahtani, S; Alsultan, A, 2019)	0.51
" The objective of this study was to review the critical care management of patients with SE focusing on antiepileptic drugs (AEDs) as well as to determine the optimal dosing strategies of phenytoin (PHT) and predictors of its effectiveness."	( Critical Care Management of Status Epilepticus at a Tertiary Care University Hospital. Ahmed, SN; Lindqvist, T; Mahmoud, SH; Marette, V, 2019)	0.7
" Dosing of phenytoin remains a challenge for all clinicians which increase the need for such reports."	( Phenytoin-Induced Paradoxical Seizures and Blood Dyscrasias in a Patient Receiving Rapid Intravenous Infusion: A Case Report. Radhakrishnan, A; Sudarsan, P; Suresh, A; Varghese, R, 2021)	2.45
" Owing to its high pharmacokinetic variability and narrow therapeutic range, plasma level-guided dosing has become the standard."	( Dosage of phenytoin in neurocritical patients using Bayesian algorithms: a pilot study. Cabrera, S; Grandjean, J; Lagos, X; Muñoz-Pichuante, D; Villa Zapata, L, 2019)	0.92
" Weight-based dosing was capped at 75 kg."	( The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus. Bleck, TP; Chamberlain, JM; Cloyd, JC; Cock, HR; Coles, LD; Conwit, RA; Elm, JJ; Fountain, NB; Kapur, J; Lowenstein, DH; Sathe, AG; Shinnar, S; Silbergleit, R, 2020)	0.81
"To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation."	( First-line medication dosing in pediatric refractory status epilepticus. Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020)	0.56
" We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation."	( First-line medication dosing in pediatric refractory status epilepticus. Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020)	0.56
" Low total BZD dosing was associated with decreased likelihood of Seizure cessation."	( First-line medication dosing in pediatric refractory status epilepticus. Abend, NS; Amengual-Gual, M; Anderson, A; Arya, R; Brenton, JN; Carpenter, JL; Chapman, K; Clark, J; Farias-Moeller, R; Gaillard, WD; Gaínza-Lein, M; Glauser, T; Goldstein, JL; Goodkin, HP; Guerriero, RM; Kapur, K; Lai, YC; Loddenkemper, T; McDonough, TL; Mikati, MA; Morgan, LA; Novotny, EJ; Ostendorf, AP; Payne, ET; Peariso, K; Piantino, J; Riviello, JJ; Sannagowdara, K; Tasker, RC; Tchapyjnikov, D; Topjian, A; Vasquez, A; Wainwright, MS; Wilfong, A; Williams, K, 2020)	0.56
" Furthermore, the serum levetiracetam concentration in patients with intraoperative seizures was below the 95% confidence interval (CI) of the regression line whereas the serum phenytoin concentration of two patients with seizures was within the 95% CI, indicating that evaluating the serum levetiracetam concentration against the BSA and eGFR-adjusted dosage may be useful in preventing intraoperative seizures during awake craniotomy by allowing prediction of the seizure risk and enabling more accurate dosage calibration."	( Utility of monitoring the serum levetiracetam concentration for intraoperative seizure control during awake craniotomy. Kawaguchi, K; Kikuchi, M; Kushihara, Y; Otani, R; Shinoura, N; Yamada, R, 2021)	0.81
" Similar dose-related responses were seen following the week-long dosing protocol for carbamazepine, phenobarbital, and phenytoin, and these responses were associated with drug levels that were in the human therapeutic range."	( Chronic limbic epilepsy models for therapy discovery: Protocols to improve efficiency. Bertram, EH; Edelbroek, P, 2021)	0.83
" In order to name some, the administration of once-daily dosing of phenytoin or the coadministration of carnitine with valproic acid would be preferable to avoid iatrogenic refractoriness."	( The role of efflux transporters and metabolizing enzymes in brain and peripheral organs to explain drug-resistant epilepsy. Fagiolino, P; Vázquez, M, 2022)	0.96
" The aim of this study was to compare the pharmacokinetic parameters of Bu after oral dosing between patients receiving phenytoin and those receiving levetiracetam prophylaxis."	( Decreased Systemic Busulfan Exposure After Oral Dosing With Concomitant Levetiracetam Compared With Phenytoin. Artul, T; Efrati, E; Henig, I; Kurnik, D; Lurie, Y; Nassar, L; Scherb, I; Yehudai-Ofir, D; Zuckerman, T, 2022)	1.15
" The objectives of this study are to develop an ex-vivo in-vivo correlation (EVIVC) model to predict drug clearance for commonly used antiepileptics and to evaluate similarity in drug extraction across different CRRT modalities to extrapolate dosing recommendations."	( Development and Use of an Ex-Vivo In-Vivo Correlation to Predict Antiepileptic Drug Clearance in Patients Undergoing Continuous Renal Replacement Therapy. Armahizer, M; Badjatia, N; Gobburu, JV; Gopalakrishnan, M; Kalaria, SN; McCarthy, P, 2022)	0.72
" As a general rule, these interactions can be managed by careful evaluation of clinical response and, when indicated, individualized dosage adjustments guided by measurement of drugs serum concentrations, especially if pharmacokinetic interactions may cause any change in seizure control or signs of toxicity."	( Pharmacokinetic Interactions Between Antiseizure and Psychiatric Medications. Franco, V; Zaccara, G, 2023)	0.91
" The inclusion of PMR in future dosing algorithms of CYP2C9 substrates characterized by a narrow therapeutic window should be encouraged and further investigated."	( Phenytoin Metabolic Ratio, a Marker of CYP2C9 Activity, is Superior to the CYP2C9 Genotype as a Predictor of (S)-Warfarin Clearance. Adar, L; Bialer, M; Blotnick, S; Caraco, Y; Muszkat, M; Shaul, C, 2022)	2.16
" Patients were divided into two groups, those who were dosed using their AdjBW versus those dosed using ABW."	( Evaluation of phenytoin loading doses in overweight patients using actual versus adjusted body weight. Coppiano, LS; Keats, K; Powell, R; Rocker, J; Waller, J, 2022)	1.08
" We aim to characterize the optimal levetiracetam dosage for seizure prophylaxis."	( Levetiracetam dosing for seizure prophylaxis in neurocritical care patients. Ansari, S; Davis, GE; Findlay, MC; Hawryluk, GWJ; Hedges, A; Menacho, ST; Wolfe, BM, 2023)	0.91
"Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing >1000-mg TDD."	( Levetiracetam dosing for seizure prophylaxis in neurocritical care patients. Ansari, S; Davis, GE; Findlay, MC; Hawryluk, GWJ; Hedges, A; Menacho, ST; Wolfe, BM, 2023)	0.91
" In such situations, the phenytoin dosage must be decreased and monitored closely."	( Phenytoin Intoxication in a Patient Receiving a Therapeutic Dose for Postoperative Seizure Prophylaxis: A Case Study. Chomchai, S; Mekavuthikul, P; Phuditshinnapatra, J; Prasertsup, W, 2023)	2.66