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

20 patients with Parkinson's disease and a fluctuating response to chronic treatment with conventional L-dopa preparations participated in an open randomized trial comparing two sustained-release L-dopa preparations (Madopar HBS, Sinemet CR4). While a majority (15 patients, 7 on Madopar HBS and 8 on Sinemet CR4) showed a favourable response after 2 months of slow-release L-dopa treatment the clinical benefit remained stable in only 2 patients on Madopar HBS and 3 patients on Sinemet CR4 over the entire follow-up period of 12 months. Reasons for treatment failure were increased peak-dose or biphasic dyskinesias or prolonged "off"-periods. This preliminary study failed to demonstrate clinically significant advantages of one slow-release principle over the other.
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PMID:Comparative efficacy of two oral sustained-release preparations of L-dopa in fluctuating Parkinson's disease. Preliminary findings in 20 patients. 157 Oct 80

Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time. Sinemet CR4 offers a theoretically attractive method of achieving gradual sustained release of levodopa over time which may be more physiological to striatal dopamine receptors in the early stages of the disease. This study evaluated 20 patients with moderate to severe Parkinson's disease who were treated with Sinemet CR4 over a 1-year period. Eleven patients completed the full year on therapy, and nine subjects withdrew. Of the withdrawals, two subjects died from non-Parkinson's disease-related illness, three showed no therapeutic benefit, and four responded well for a minimal 6-month period, but then lost therapeutic benefit and developed more severe dystonias. A higher overall levodopa dosage was required by all patients, and side-effects of levodopa were still present in most patients. However, the nocturnal benefit of this long-acting preparation was observed by all the patients in the study. Slow onset of action of Sinemet CR4 resulted in early-morning immobility. Sinemet CR4 cannot replace standard Sinemet, but appears to be a useful form of adjunct therapy in selected patients.
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PMID:Sinemet (CR4): an open-label study in moderately severe Parkinson's disease. 186 61

Twenty patients with moderately severe Parkinson's disease entered an open study of the efficacy and safety of a slow release preparation containing levodopa 200 mg and carbidopa 50 mg per tablet ('Sinemet CR4'). Following an initial four week baseline stabilisation period on conventional 'Sinemet' tablets, the patients were transferred to 'Sinemet CR4' and observed at intervals over the next 12 months. Fifteen patients completed the full year observation period. When compared with the baseline period, treatment with 'Sinemet CR4' was associated with longer periods of functional improvement and less fluctuation of response following each dose. The median (range) dose frequency was reduced from three (three-12) to two (two-seven) times daily (p less than 0.001) on 'Sinemet CR4' although median (range) total daily dose of levodopa was increased from 700 (375-2525) to 800 (400-2800) mg without any increase in adverse effects. Three patients developed peripheral neuropathy while receiving Sinemet CR4, but the association with this therapy is unclear. Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'.
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PMID:Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety. 195 26

Sinemet-controlled release (CR4) consisting of 50 mg carbidopa/200 mg levodopa was compared with Sinemet 25/100 in 24 Parkinson's disease (PD) patients during a 16-week double-blind cross-over study. The mean age of the patients was 66.2 years, their mean duration of PD was 9.3 years. All of the patients had response fluctuations consisting mainly of the 'wearing-off' phenomenon. Some of the patients also experienced the 'on-off' phenomenon. All patients were evaluated using the unified Parkinson disease rating scale. The following significant differences were noted on Sinemet CR4. More patients noted a decrease in dyskinesias and response fluctuations; more patients experienced a decrease in stage when 'on'; more patients were 'on' longer during the day, and more patients were globally improved. The mean number of doses per day were significantly less on Sinemet CR4 (mean 5.0, range 3-8) than on Sinemet 25/100 (mean 6.2, range 4-11 doses/day). The mean dose of levodopa in Sinemet CR4 was 1,186 +/- 458 mg and the mean dose of carbidopa was 797 +/- 115 mg. The mean dose of levodopa in Sinemet 25/100 was 873 +/- 304 mg and the mean dose of carbidopa was 218 +/- 76 mg. This study indicates that Sinemet CR4 is a useful addition for patients with response fluctuations.
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PMID:Randomized double-blind cross-over study of Sinemet-controlled release (CR4 50/200) versus Sinemet 25/100 in Parkinson's disease. 234 Aug 38

"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.
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PMID:Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations. 268 15

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

Sixteen patients with advanced Parkinson's disease (PD) and motor fluctuations were evaluated throughout 12 months of open label therapy on CR4-Sinemet. Reduced dosage frequency and significant motor improvement with reduced fluctuation occurred and were maintained with CR4-Sinemet compared with baseline on Sinemet. In a double-blind protocol using CR4-Sinemet in 20 stable PD patients, CR4-Sinemet was given twice daily and compared with Sinemet given four times daily. Patients remained stable without improvement or deterioration when the long-acting drug was substituted at 50% frequency. Plasma levodopa levels with CR4-Sinemet were smoother than with Sinemet. Although some patients receiving CR4-Sinemet found they functioned more slowly in the morning, the easier dosing schedule and improved amount of "on" time in fluctuators suggest that this formulation may become increasingly useful in managing PD.
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PMID:Controlled-release carbidopa/levodopa (CR4-Sinemet) in Parkinson's disease patients with and without motor fluctuations. 329 Jul 6

Five patients with advanced Parkinson's disease and fluctuations in therapeutic response to levodopa participated in, and four completed, an open label study of the efficacy of Sinemet CR5. Reductions in the number of daily doses and "off" periods as well as the increase in interdose interval and percent "on" time versus standard Sinemet were comparable to those achieved with Sinemet CR4 in these same patients. As compared with Sinemet CR4, there was a greater delay in the occurrence of peak plasma levodopa concentrations, and relative bioavailability was reduced. Sinemet CR5 appears to offer no advantages over Sinemet CR4 in the treatment of response fluctuations in Parkinson's disease.
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PMID:Controlled-release levodopa/carbidopa. III: Sinemet CR5 treatment of response fluctuations in Parkinson's disease. 337 25

Sixteen patients with Parkinson's disease and therapeutic response fluctuations entered an open-label trial of a controlled-release carbidopa/levodopa preparation, Sinemet CR4. Sinemet CR4 behaved as a slow release preparation. At the end of 6 weeks CR4 treatment, there was an increase in percent "on" time and mean interdose interval; the number of daily doses and "off" periods were diminished and a slight reduction in the variability of plasma levodopa levels was observed. Overall benefit waned over the next 6 months, despite addition of standard levodopa or Sinemet to overcome the delayed onset of antiparkinsonian effect of CR4 which resulted from prolongation in the Tmax for levodopa. The major benefits of CR4 were reduction in off time and in the number of daily off periods, with fewer levodopa doses per day and prolongation of the interdose interval.
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PMID:Controlled-release levodopa/carbidopa. II. Sinemet CR4 treatment of response fluctuations in Parkinson's disease. 365 64


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