entacapone and carbidopa--levodopa-drug-combination

Levodopa remains the most effective treatment for Parkinson's disease and is considered the gold standard therapy. However, disease progression and changes in the gastrointestinal tract result in a declining window of treatment response in a majority of patients. Efforts have been made recently to improve levodopa bioavailability either by developing more effective oral formulations or by innovating routes of administration (intestinal infusion, transcutaneous or inhaled levodopa). IPX066 is a novel levodopa-carbidopa (LD/CD) oral formulation combining immediate-release (IR) and extended-release (ER) LD/CD recently approved in the USA and the EU. Levodopa-carbidopa intestinal gel (LCIG) is an approved therapy consisting of a suspension of levodopa and carbidopa infused directly into the proximal jejunum via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube through a portable infusion pump. Ongoing studies are evaluating the 'accordion pill' (AP09004), an ER LD/CD formulation with gastroretentive properties. ND0612 is a proprietary liquid formulation of LD/CD that enables subcutaneous administration via a small patch-pump device, and CVT-301 is a levodopa inhalation powder with rapid onset of action; both are currently in active studies. Other novel formulations have been discontinued, including DM-1992, which is a bilayer formulation containing an IR LD/CD layer and an ER LD/CD layer with gastroretentive properties, and XP21279, a novel oral levodopa prodrug that is absorbed from the small and large intestine by high-capacity nutrient transporters expressed throughout the gastrointestinal system. ODM-101 is a new oral formulation of levodopa/carbidopa/entacapone that contains a higher amount of carbidopa (65 or 105 mg), but no active studies are underway. The current review aims to summarize the pharmacokinetic aspects, clinical efficacy, and potential adverse events of novel levodopa formulations currently available or under development.

Topics: Antiparkinson Agents; Carbidopa; Catechols; Chemistry, Pharmaceutical; Drug Combinations; Humans; Levodopa; Nitriles; Parkinson Disease

The unique needs of patients with Parkinson disease challenge staff when such patients are admitted to hospitals or nursing facilities. Prolongation of the hospital stay, falls with injuries, fainting, or declining motor function may result from therapeutic misadventures or failure to anticipate common problems. Staff familiarity with Parkinson disease, and especially carbidopa-levodopa dosing and dynamics, may prevent such problems and streamline hospital and nursing home care.

Topics: Amantadine; Antiparkinson Agents; Carbidopa; Catechols; Dopamine Agonists; Drug Administration Schedule; Drug Combinations; Hospitalization; Humans; Levodopa; Monoamine Oxidase Inhibitors; Nitriles; Nursing Care; Parkinson Disease

Parkinson disease progression is associated with the development of levodopa short-duration responses and dyskinesias, as well as gait freezing. Levodopa dose adjustment and adjunctive treatment with dopamine agonists form the major therapeutic strategies. Catechol O-methyltransferase inhibitors are also appropriate considerations, whereas other drugs, including selegiline, amantadine, anticholinergic agents, and propranolol, have a more minor role.

Topics: Amantadine; Antiparkinson Agents; Benzophenones; Carbidopa; Catechol O-Methyltransferase Inhibitors; Catechols; Cholinergic Antagonists; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Combinations; Dyskinesia, Drug-Induced; Enzyme Inhibitors; Humans; Levodopa; Nitriles; Nitrophenols; Parkinson Disease, Secondary; Propranolol; Randomized Controlled Trials as Topic; Selegiline; Tolcapone

ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations.. This was a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics of ND0612 in PD patients on an optimized oral levodopa regimen and experiencing ≥2 h/day of OFF time. During Period-1, patients received their current standard of care (SoC) levodopa/carbidopa and were randomized (2:1) to 14 days treatment with adjunct ND0612 (daily levodopa/carbidopa dose of 270/63 mg) or placebo infusion +SoC. During Period-2, 16 patients were randomized to receive 7 days treatment with ND0612 or ND0612 plus oral entacapone. Reduction in OFF time was analyzed as an exploratory measure using a futility design with a predefined margin of 1.6 h.. ND0612 was well-tolerated; most patients experienced infusion site nodules (95% vs. 56% with placebo), which all resolved without sequelae. Patients treated with adjunct ND0612 during Period-1 avoided deep troughs in levodopa plasma levels and had a decreased fluctuation index versus placebo (1.6 ± 0.5 vs 3.1 ± 1.6 at end of Period-1, respectively). In Period-2, the coadministration of entacapone with continuous ND0612 SC infusion translated to an increase in mean levodopa AUC. Levodopa/carbidopa infusion with ND0612 was generally well-tolerated and resulted in reduced fluctuations in plasma levodopa concentrations when given with SoC oral levodopa. ND0612 met the efficacy endpoint for the futility design.

Topics: Administration, Oral; Aged; Antiparkinson Agents; Carbidopa; Catechols; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Infusions, Subcutaneous; Levodopa; Male; Middle Aged; Motor Activity; Nitriles; Parkinson Disease; Proof of Concept Study; Treatment Outcome

Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through intrajejunal infusion. The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. A non-linear mixed-effects model of levodopa pharmacokinetics was developed using plasma concentration data from a double-blind, cross-over study of LCIG compared with LECIG in patients with advanced Parkinson's disease (n = 11). All patients were genotyped for rs4680 (polymorphism of the COMT gene), rs921451 and rs3837091 (polymorphisms of the DDC gene). The final model was a one compartment model with a high fixed absorption rate constant, and a first order elimination, with estimated apparent clearances (CL/F), of 27.9 L/h/70 kg for LCIG versus 17.5 L/h/70 kg for LECIG, and apparent volume of distribution of 74.4 L/70 kg. Our results thus suggest that the continuous maintenance dose of LECIG, on a population level, should be decreased by approximately 35%, to achieve similar drug exposure as with LCIG. An effect from entacapone was identified on all individuals, regardless of COMT rs4680 genotype. The individuals with higher DDC and COMT enzyme activity showed tendencies towards higher levodopa CL/F. The simultaneous administration of entacapone to LCIG administration results in a 36.5% lower apparent levodopa clearance, and there is a need for lower continuous maintenance doses, regardless of patients' COMT genotype.

Topics: Carbidopa; Catechol O-Methyltransferase; Catechols; Cross-Over Studies; Dopa Decarboxylase; Double-Blind Method; Drug Combinations; Drug Delivery Systems; Female; Gels; Genotype; Humans; Levodopa; Male; Models, Biological; Nitriles; Parkinson Disease; Polymorphism, Genetic

The addition of oral entacapone to levodopa-carbidopa intestinal gel treatment leads to less conversion of levodopa to 3-O-methyldopa, thereby increasing levodopa plasma concentration. The objective of this study was to compare systemic levodopa exposure of the newly developed levodopa-entacapone-carbidopa intestinal gel after a 20% dose reduction with levodopa exposure after the usual levodopa-carbidopa intestinal gel dose in a randomized crossover trial in advanced Parkinson's disease patients.. In this 48-hour study, 11 patients treated with levodopa-carbidopa intestinal gel were randomized to a treatment sequence. Blood samples were drawn at prespecified times, and patient motor function was assessed according to the treatment response scale.. Systemic exposure of levodopa did not differ significantly between treatments (ratio, 1.10 [95% confidence interval, 0.951-1.17]). Treatment response scale scores did not significantly differ between treatments (P = 0.84).. Levodopa-entacapone-carbidopa intestinal gel allowed a lower amount of levodopa administration and was well tolerated. Long-term studies are needed to confirm the results. © 2016 International Parkinson and Movement Disorder Society.

Topics: Aged; Antiparkinson Agents; Carbidopa; Catechols; Cross-Over Studies; Drug Combinations; Female; Humans; Infusions, Parenteral; Levodopa; Male; Nitriles; Parkinson Disease; Treatment Outcome

Entacapone is frequently used together with levodopa/carbidopa (LC) and levodopa/benserazide (LB) in the treatment of Parkinson's disease (PD) patients with wearing-off symptoms. It is generally assumed that the effects of entacapone are independent of the type of decarboxylase inhibitor used, but there is very little published data available on the efficacy of entacapone administered with LB versus LC. We have performed a pooled analysis of three randomized, double-blind, 6-month, phase III studies to compare the treatment effects of entacapone (compared to placebo) in PD patients receiving LC or LB. A total of 551 PD patients experiencing wearing-off were included in the analysis. 300 patients were on LB and 251 on LC at baseline. At 6 months, entacapone (compared to placebo) improved mean daily OFF-time in patients on LB and LC by 0.76 (p = 0.016) and 0.95 (p = 0.011) hours, respectively. The corresponding improvements in ON-time were 0.97 (p = 0.002) and 0.83 h (p = 0.022), respectively. The treatment effects of entacapone both in LB and LC users were statistically significant (p < 0.05) also in UPDRS II and III scores, except in UPDRS II scores in patients receiving LC (p = 0.20). None of the treatment effects of entacapone were statistically significantly different between patients receiving LB or LC. Reported adverse events were comparable between LB and LC users. We conclude that entacapone provided comparable benefits in PD patients with wearing-off symptoms using either LB or LC.

Topics: Antiparkinson Agents; Benserazide; Carbidopa; Catechol O-Methyltransferase Inhibitors; Catechols; Data Interpretation, Statistical; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Retrospective Studies; Treatment Outcome

Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours.. To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting.. Patients had ≥2.5 hours/day of "off" time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided.. Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily "off" time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE.. Among PD patients with substantial "off" time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.

Topics: Aged; Antiparkinson Agents; Carbidopa; Catechols; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Levodopa; Male; Middle Aged; Nitriles; Outcome Assessment, Health Care; Parkinson Disease; Treatment Outcome

IPX066, an investigational extended-release carbidopa-levodopa (CD-LD) preparation, has demonstrated a rapid attainment and prolonged maintenance of therapeutic LD plasma concentrations in advanced Parkinson's disease (PD). This phase-3 crossover study assessed its efficacy and safety vs. CD-LD plus entacapone (CL + E).. At baseline, all patients had motor fluctuations despite a stable regimen of CL + E or CD-LD-entacapone combination tablets (CLE). The study included a 6-week conversion from CL + E or CLE to IPX066, followed by two 2-week, double-blind crossover treatment periods in randomized order, one on IPX066 (and placebo CL + E), the other on CL + E (and placebo IPX066), separated by 1-week open-label IPX066 treatment. The primary efficacy measure was mean percent daily "off" time during waking hours (from patient diaries).. Of 91 randomized patients, 84 completed the study. Their median daily LD dosage was 1495 mg from IPX066 and 600 mg from CL + E, corresponding, after correction for bioavailability, to an approximately 22% higher LD exposure on IPX066. Compared with CL + E, IPX066 demonstrated a lower percent "off" time (24.0% vs. 32.5%; p < 0.0001), lower "off" time (3.8 vs. 5.2 h/day; p < 0.0001), and higher "on" time without troublesome dyskinesia (11.4 vs. 10.0 h/day; p < 0.0001). Other endpoints, including patient-reported treatment preference, also favored IPX066 (p < 0.05). During double-blind treatment, 20.2% and 13.6% of patients reported adverse events on IPX066 and CL + E, respectively. The most common were dyskinesia (4 patients), insomnia (3), and confusional state (3) for IPX066, and fall (2) for CL + E.. In advanced PD, IPX066 showed improved efficacy, compared with CL + E, and appeared to be well tolerated.

Topics: Aged; Antiparkinson Agents; Carbidopa; Catechols; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Treatment Outcome; Walking

Several cases of syndrome of inappropriate antidiuresis induced by anti-Parkinson agents have been reported. Our previous study demonstrated that pergolide and pramipexole stimulated elevation of plasma arginine vasopressin (AVP) levels in some patients with Parkinson's disease (PD), but that levodopa/carbidopa (300/30 mg/day) did not affect plasma AVP levels in treatment-naïve PD patients. On the basis of the binding profile of ropinirole to monoamine receptors, we hypothesized that ropinirole does not stimulate AVP secretion. The aim of this study was to test this hypothesis.. Inclusion criteria were patients with probable PD suffering from a wearing-off phenomenon and who had been treated using levodopa/carbidopa with or without entacapone, but not with other classes of anti-Parkinson agents. Patients were excluded if they had at least one condition that could be associated with high AVP levels. Ropinirole was initiated at 0.5 mg 3 times daily, and daily dosages were increased by 1.5 mg/day on a biweekly basis up to 6 mg/day. Plasma AVP levels were determined every two weeks. Effects of escalating ropinirole dosage on plasma AVP levels were evaluated using a one-way analysis of variance for repeated measures, an a priori Dunnett multiple comparison test, and a regression analysis.. Of 16 patients enrolled, 11 patients (four males and seven females) completed the study. There was no statistically significant dose-response relationship between the ropinirole dosage and plasma AVP levels.. A minimal therapeutic dosage of ropinirole did not affect plasma AVP levels in patients with PD taking levodopa.

Topics: Aged; Arginine Vasopressin; Carbidopa; Catechols; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Humans; Inappropriate ADH Syndrome; Indoles; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease

Elevation of plasma total homocysteine concentrations were observed in levodopa/dopa decarboxylase inhibitor (DDI)-treated patients with Parkinson's disease (PD). Degradation of levodopa to 3-O-methyldopa via the enzyme catechol-O-methyltransferase (COMT) is a methyl group demanding reaction. It generates homocysteine from the methyl group donor methionine. But there are inconsistent outcomes, as most investigators determined homocysteine after an overnight washout of levodopa. They did not consider the acute effects of levodopa/DDI intake in relation with COMT inhibition on homocysteine bioavailability. The purpose of this study is to measure levels of homocysteine, levodopa, and its metabolite 3-O-methyldopa in plasma after reiterated oral levodopa/DDI administration with and without the COMT-inhibitor entacapone (EN). Sixteen PD patients received 100 mg levodopa/carbidopa three times on day 1 and with EN on day 2 under standardized conditions. Homocysteine concentrations increased on day 1 and generally over the whole interval. No significant ascent of homocysteine appeared on day 2 only. Levodopa bioavailability was higher on day 2 due to the COMT inhibition. No change of 3-O-methyldopa appeared between both days. The correlation coefficients between homocysteine, levodopa, and 3-O-methyldopa were higher on day 1 than on day 2. Rise of homocysteine does not only depend on the oral levodopa dose, but also on the acute intake of levodopa/DDI with or without COMT inhibition. Measurements of homocysteine should consider acute repeated levodopa/DDI applications, as homocysteine and metabolically related 3-O-methyldopa accumulate due to their long plasma half-life in contrast to short-living levodopa.

Topics: Aged; Antiparkinson Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Biological Availability; Carbidopa; Catechol O-Methyltransferase Inhibitors; Catechols; Drug Combinations; Drug Therapy, Combination; Female; Half-Life; Homocysteine; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Tyrosine

Controlled-release levodopa/carbidopa (CR-LC) is often used to provide prolonged control of night-time motor symptoms in patients with Parkinson's disease (PD). Levodopa/carbidopa/entacapone (LCE) provides higher bioavailability of levodopa compared with levodopa/carbidopa formulations and has been shown to be effective in PD patients with wearing-off symptoms. The aim of this study was to compare the bioavailability of levodopa after a single evening dose (administered at 10 p.m.) of LCE 200 or CR-LC 200.. This was an open-label, randomized, crossover study in healthy subjects. The main pharmacokinetic (PK) parameters were AUC, Cmax, C6h and t1/2 of levodopa.. A single evening dose of LCE 200 was associated with significantly better bioavailability compared with CR-LC 200. In line with increased bioavailability of levodopa, LCE 200 induced more nausea.. The results of this study demonstrate that a single bedtime dose of LCE 200 provides higher bioavailability of levodopa compared to CR-LC 200.

Topics: Adolescent; Adult; Antiparkinson Agents; Area Under Curve; Biological Availability; Carbidopa; Catechols; Cross-Over Studies; Delayed-Action Preparations; Drug Administration Schedule; Drug Combinations; Female; Half-Life; Humans; Levodopa; Male; Nitriles; Time Factors; Young Adult

Entacapone is a specific, potent, peripherally acting catechol-O-methyltransferase (COMT) inhibitor. It has been shown to improve the bioavailability of plasma levodopa and extend its clinical effect when used as an adjunct to standard levodopa preparations, but there is little experience of the effect of entacapone on controlled release levodopa preparations.. A double blind, placebo controlled, single dose, randomised, cross over trial was performed in 14 patients with Parkinson's disease with motor fluctuations to investigate the clinical effect of a single dose of entacapone (200 mg) when administered with either standard levodopa-carbidopa (Sinemet) or controlled release levodopa-carbidopa preparations (Sinemet CR).. When entacapone was administered with standard Sinemet the duration of the clinical response to standard Sinemet was longer in comparison with the response after placebo (p=0.02). Moreover, in the same patients, entacapone significantly increased the duration of the clinical response to Sinemet CR (p=0.05) without prolonging the latency of response or enhancing dyskinesias.. These data confirm the clinical efficacy of entacapone-standard Sinemet combination. They also indicate that adding entacapone to controlled release levodopa preparations might provide a useful treatment option in patients with Parkinson's disease with motor fluctuations. A double blind clinical trial with a chronically administered entacapone-Sinemet CR combination is, however, required to verify this viewpoint.

Topics: Adult; Aged; Antiparkinson Agents; Biological Availability; Carbidopa; Catechol O-Methyltransferase Inhibitors; Catechols; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Enzyme Inhibitors; Female; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease

We studied the effect of entacapone, a catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of a controlled-release (CR) levodopa-carbidopa preparation (Sinemet CR) in an open, randomized trial in 12 healthy male volunteers. The inhibition of soluble COMT (S-COMT) in red blood cells (RBCs) was also measured. Single graded doses of entacapone (100-800 mg) were administered concomitant with a single oral dose of CR levodopa, or CR levodopa was given without entacapone (control treatment), at least 1 week apart. Plasma concentrations of levodopa, 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), carbidopa, and entacapone were determined for pharmacokinetic calculations. Entacapone decreased dose-dependently the activity of S-COMT in RBCs with a maximal inhibition of 66% after the highest dose (800 mg). Entacapone increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was highest (33%) after the 400-mg dose. Entacapone did not influence time to maximal concentration (Tmax) of levodopa. Entacapone was absorbed faster than levodopa from the CR preparation. The AUCs of 3-OMD and HVA decreased and that of DOPAC increased dose-dependently after entacapone, maximally by 69, 38, and 74%, respectively. Higher doses of entacapone (400 mg and 800 mg) decreased the AUC, but not Tmax of carbidopa. Over the dose range studied, entacapone was well tolerated. Entacapone is an effective COMT inhibitor. It improves the pharmacokinetic profile of levodopa when used in combination with a CR levodopa preparation, as it does with a standard levodopa preparation. The results justify further clinical studies with entacapone in combination with CR preparations of levodopa.

Topics: Adult; Carbidopa; Catechols; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Combinations; Enzyme Inhibitors; Humans; Levodopa; Male; Nitriles; Reference Values

Topics: Antiparkinson Agents; Carbidopa; Catechols; Combined Modality Therapy; Deep Brain Stimulation; Drug Combinations; Drug Therapy, Combination; Fever; Humans; Hyperkinesis; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease

Topics: 5-alpha Reductase Inhibitors; Aged; Antiparkinson Agents; Benzothiazoles; Cabergoline; Carbidopa; Catechols; Drug Combinations; Drug Monitoring; Drug Therapy, Combination; Ergolines; Finasteride; Gambling; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Pramipexole; Treatment Outcome; Video Games

Topics: Antiparkinson Agents; Apomorphine; Carbidopa; Catechols; Drug Combinations; Drugs, Generic; Humans; Indans; Levodopa; Nitriles; Parkinson Disease

Topics: Antiparkinson Agents; Carbidopa; Catechols; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Levodopa; Neurologic Examination; Nitriles; Parkinson Disease; Randomized Controlled Trials as Topic; Receptors, Dopamine

The short plasma half-life limits the antiparkinsonian efficacy of levodopa/carbidopa (LD/CD). Administration of LD/CD with the catechol-O-methyltransferase inhibitor entacapone in one tablet (LCE) may extend plasma half-life of LD and thus its effect on motor symptoms in patients with Parkinson's disease (PD). The objectives of this study were to monitor the motor response to a switch from LD/CD to LCE by a simultaneous performance of an instrumental motor test and rating of motor symptoms and to compare the LD plasma behavior between both conditions in terms of stability. Twenty-one treated PD patients received LD/CD and then the identical oral LD dosage of LCE within a standardized setting on 2 consecutive days. Rating better reflected the motor improvement after LD application than the instrumental test. Motor symptoms of PD patients decreased significantly more during the LCE than the LD/CD condition, probably due to significantly higher LD plasma levels and a significantly less pronounced fall of the LD concentrations following the second LD intake. Our study shows a more stable LD plasma behavior during LCE intake and accordingly a better effect on motor symptoms according to rating outcomes and motor test results to a lesser extent.

Topics: Adult; Aged; Antiparkinson Agents; Carbidopa; Catechol O-Methyltransferase Inhibitors; Catechols; Dopamine Agonists; Drug Combinations; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease

Entacapone increased the duration of action of carbidopa-levodopa and resulted in longer periods of symptomatic relief in a patient with restless legs syndrome. The only side effect was nausea.

Topics: Antiparkinson Agents; Carbidopa; Catechols; Delayed-Action Preparations; Drug Combinations; Drug Therapy, Combination; Female; Humans; Levodopa; Middle Aged; Neurologic Examination; Nitriles; Restless Legs Syndrome