Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety and efficacy of Sinemet CR were studied in an open-label, 52-week trial. The study was completed by 156 mildly to moderately ill Parkinson's patients (primarily Hoehn and Yahr stage II to III) at 10 sites. Patients had their treatment optimized on standard Sinemet prior to beginning Sinemet CR treatment. Following titration, there was a median reduction in dosing frequency of 25% (from 4.1 to 3.2 doses/day) relative to the standard Sinemet baseline. Total daily levodopa dosage increased from 623 to 808 mg/day (+33%), a factor consistent with the lower bioavailability of the controlled-release formulation. Mean efficacy scores on the New York University Parkinson's Disease Scale decreased from 7.4 at the end of baseline to 5.8 at 12 weeks, a decline of 20%. The scores remained at this level throughout 52 weeks of treatment. At the end of 1 year of treatment, 60% of patients rated themselves as improved, while physicians rated 64% of the patients as improved. Adverse experiences were similar to those reported by patients taking standard levodopa preparations. Two thirds of the reported adverse experiences occurred within the 1st 3 months of Sinemet CR therapy, indicating that increased length of exposure to Sinemet CR was not associated with an increasing incidence of adverse experiences.
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PMID:An open multicenter long-term treatment evaluation of Sinemet CR. Sinemet CR Multicenter Study Group. 268 46

The pharmacokinetics of Sinemet CR, a controlled-release formulation containing carbidopa and levodopa, were investigated in healthy young and elderly volunteers and in patients with Parkinson's disease. Sinemet CR produced more sustained plasma levels of levodopa, carbidopa, and 3-O methyldopa than did conventional Sinemet. In elderly subjects, the corresponding steady-state plasma levels fluctuated in narrower ranges with Sinemet CR than those following the administration of Sinemet. Results indicate a levodopa bioavailability of 71% for Sinemet CR, in contrast to a bioavailability of 99% for Sinemet for these subjects. The carbidopa bioavailability of Sinemet CR was 58% relative to that of Sinemet. Systemic decarboxylase inhibition was comparable between the 2 regimens as indicated by the renal clearance of levodopa. The absorption of levodopa was slower and more protracted with Sinemet CR than with Sinemet. Food increased the levodopa bioavailability of Sinemet CR. This increase was attributed to an increased gastric retention time. No dose-dumping occurred with Sinemet CR in either the nonfasting or the fasting state. Levodopa bioavailability was lower in young volunteers than in elderly volunteers. This was attributed to an age-related decrease in gastric emptying and in 1st-pass metabolic decarboxylation in the gastrointestinal (GI) tract. In parkinsonian patients, as in healthy subjects, the Sinemet CR formulation produced more sustained levodopa plasma levels. These patients required a higher total daily dosage of Sinemet CR than of Sinemet for control of parkinsonian symptoms, but less frequent dosing was required during chronic therapy. Peak plasma levodopa levels increased proportionately with increasing Sinemet CR dosage. These observations were consistent with the pharmacokinetic characteristics of the formulation.
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PMID:Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. 268 49

Controlled-release carbidopa/levodopa 50/200 (Sinemet CR) and standard carbidopa/levodopa (Sinemet 25/100) were compared in a multicenter double-blind trial involving 202 patients with advanced Parkinson's disease and motor response fluctuations. Treatment with Sinemet CR significantly reduced daily "off" time. According to both physician and patient global ratings, patients showed significant improvements with Sinemet CR compared to treatment with standard Sinemet. Patients preferred Sinemet CR treatment by a ratio of approximately 2 to 1. Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%. The safety profiles of the 2 formulations were similar. We conclude that Sinemet CR is superior to standard Sinemet for many patients with advanced Parkinson's disease, although it does not solve the problem of fluctuating motor performance.
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PMID:Multicenter controlled study of Sinemet CR vs Sinemet (25/100) in advanced Parkinson's disease. 268 52

Levodopa combined with carbidopa (Sinemet) remains the most effective approach to the symptomatic relief of Parkinson's disease. Over time, however, an increasing number of parkinsonian patients evidence motor response complications, notably abnormal involuntary movements and motor fluctuations. Clinical pharmacologic studies suggest that these phenomena may arise as a consequence of factors reflecting both natural disease progression and levodopa toxicity. Simple wearing-off responses appear primarily related to advancing degenerative changes afflicting the dopamine system. The appearance of peak-dose dyskinesias and complex, random motor fluctuations of the on-off type, on the other hand, may signal secondary postjunctional changes arising as a consequence of chronic intermittent excitation of postsynaptic dopamine receptors that are normally tonically stimulated. Therapeutically, prompt correction of wearing-off fluctuations can ordinarily be achieved by measures that deliver dopaminomimetics continuously to the central nervous system. In contrast, fluctuations of the on-off type initially persist despite stable circulating levodopa levels. With continuous levodopa treatment, however, the threshold for dyskinesias begins to rise and the dose-response relation shifts to the right; clinically, the severity of both dyskinesias and on-off fluctuations tends to diminish. It is thus tempting to speculate that the early and continuing treatment of Parkinson's disease with compounds providing a relatively constant level of central dopamine stimulation will preclude wearing-off phenomena and mitigate on-off fluctuations and severe dyskinesias.
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PMID:Rationale for continuous dopaminomimetic therapy of Parkinson's disease. 268 53

The combination of carbidopa and levodopa (Sinemet) is a highly effective treatment for the symptoms of Parkinson's disease. However, side effects, such as abnormal involuntary movements, fluctuations in motor performance, and "wearing off" phenomena limit its long-term usefulness in some patients. Open-label studies show that controlled-release Sinemet CR is effective in reducing motor fluctuations. This report discusses the results of a 14-week double-blind crossover study comparing the efficacy and tolerability of standard Sinemet with controlled-release Sinemet CR. Overall, there were no statistically significant differences in efficacy between Sinemet CR and standard Sinemet on any of the major efficacy measures, suggesting a clinical equivalence in terms of treating the symptoms of Parkinson's disease. The study also supports the tolerability of Sinemet CR. In summary, Sinemet CR holds the promise of reducing some disturbing side effects of long-term levodopa therapy, thus achieving optimal control of parkinsonian symptoms.
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PMID:Double-blind comparison of standard Sinemet and Sinemet CR in patients with mild-to-moderate Parkinson's disease. 268 55

Twenty-one patients with Parkinson's disease and motor fluctuations who completed a double-blind study comparing controlled-release carbidopa/levodopa (Sinemet CR4) with standard Sinemet (SS) were evaluated one year following completion of the study. Five patients remained on CR4 alone; 16 continued on CR4 plus SS, and one also required addition of bromocriptine. Patients were significantly worse (p less than 0.05) at one year compared with double-blind CR4 phase (DBCR) for nine parameters of the motor exam, six activities of daily living (ADL), Hoehn & Yahr staging, and physician's global assessment. Compared with baseline SS, patients were worse at one year for four points of the motor exam, two of mentation, behavior, and mood, and 11 parameters of ADL. Improvement at one year was noted for less action and postural tremor and decreased duration of dyskinesias for both comparison periods. There was elimination of early morning dystonia at one year over the DBCR period and more hours "on" without dyskinesias and fewer hours "on" with dyskinesias compared with baseline SS. Total levodopa dosage was not significantly changed over the year. These data suggest that, in long-term use, CR4 remains more efficacious than SS alone for Parkinson's patients experiencing motor fluctuations, although disease progression continues despite optimal medication.
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PMID:Long-term efficacy of controlled-release carbidopa/levodopa in patients with advanced Parkinson's disease. 269 Jul 30

The efficacy of Sinemet CR4 (50/200) was compared to standard Sinemet (25/100) in an open label crossover study in 22 patients with Parkinson's disease. All patients experienced end of dose failure and 11 had dyskinesia. Unified Parkinson's disease, Hoehn and Yahr, Schwab and England scores, number of hours on per day, number of hours of dyskinesia per day, daily dose of levodopa, and number of doses per day were monitored at the end of each treatment period and the results compared. The only significant difference in these parameters between the CR4 and standard Sinemet treatment periods in the entire group was a decrease in hours of dyskinesia per day. Two subgroups of CR4 responders were specifically examined. The first subgroup was characterised by a significant increase in on time per day with CR4 therapy. These patients had an older age of onset of Parkinson's disease and a shorter duration of disease and fluctuations than the rest of the patients. The second subgroup was characterised by the presence of dyskinesia with standard Sinemet therapy and a significant decrease in hours of dyskinesia per day with CR4 therapy. Both subgroups required a significantly higher daily dose of levodopa while on CR4. It is concluded that CR4 may be useful in increasing hours on per day in subgroups of Parkinson's disease patients who have less severe fluctuations. It may also be useful in decreasing the number of hours of dyskinesia per day.
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PMID:Efficacy of sinemet CR4 in subgroups of patients with Parkinson's disease. 270 40

The effect of a 2.5-fold increase in daily carbidopa intake on the bioavailability of levodopa was studied in six patients with Parkinson's disease on a low chronic regimen of carbidopa-levodopa (Sinemet) at the fixed ratio of 1:10. The extent of levodopa absorption, expressed as the area under the 11-h plasma levodopa concentration-time curve (AUC0-11 h), was not enhanced by the higher carbidopa dose. A significant increase in the AUC was found for the levodopa metabolite 3-O-methyldopa at the higher carbidopa intake. Clinical performances of individual patients were identical with both carbidopa-levodopa ratios. From these data, an adequate inhibition of peripheral decarboxylation and hence a good bioavailability of levodopa may be expected in patients taking low doses of carbidopa-levodopa, using currently available commercial preparations.
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PMID:Increased dosage of carbidopa in parkinsonian patients on low carbidopa-levodopa regimen. Effect on levodopa bioavailability. 271 68

Nineteen patients with mild-to-moderate Parkinson's disease completed a 1-year open label study of a controlled release preparation of carbidopa/L-DOPA (Sinemet CR). Twelve patients were thought to have improved compared with baseline, and only one was worse. The total daily dose of L-DOPA was not significantly changed, but dosing frequency was almost halved. Patients with complex drug schedules on standard Sinemet liked the drug most. "Wearing off" patients also benefitted from the change, whereas "on/off" patients did not do significantly better on Sinemet CR.
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PMID:An open trial of controlled release carbidopa/L-dopa (sinemet CR) for the treatment of mild-to-moderate Parkinson's disease. 274 46

We examined 50 untreated parkinsonian patients with a complaint of tremor for the presence of a resting, postural, or kinetic tremor. Tremors were recorded by an accelerometer to determine amplitude and frequency. A postural tremor was present in 92% and a resting tremor in 76%. The amplitude of postural tremor was greater than resting tremor in 50%, the same in 25%, and less in 25%. The average tremor frequency of resting and postural tremor was not significantly different. Carbidopa/levodopa reduced testing tremor in 58% and postural tremor in 46% of patients. The dopamine agonist naxoglide (PHNO) reduced resting tremor in 77% and postural tremor in 70% of patients. Postural tremor was not worsened by either drug. It is concluded that tremors in both the resting and postural positions are an integral part of the symptoms of Parkinson's disease and that both tremors have a similar frequency and pharmacological responsiveness in the early phases of the disease.
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PMID:Tremors in early Parkinson's disease. 280 93


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