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)

Seventeen patients with advanced Parkinson's disease who had fluctuations in motor performance while taking standard Sinemet (STD) 25/100 underwent daylong pharmacokinetic and clinical observation studies while taking both STD and Sinemet CR, a new controlled-release formulation containing 50 mg carbidopa and 200 mg levodopa. During treatment with Sinemet CR, there was an increase in the interdose interval, a reduction in the number of medication doses taken each day, an increase in total "on" time, and a reduction in the number of "off" episodes. Total daily levodopa intake was greater with Sinemet CR, although the bioavailability of levodopa and carbidopa from the two preparations was equivalent. The variability in plasma levodopa levels was significantly less with Sinemet CR. The slower release of drug from Sinemet CR was reflected in a prolongation of the Tmax for levodopa and a prolongation of the interval from Tmax to the succeeding trough levodopa level. Clinically, peak antiparkinsonian effect occurred later and lasted longer with the CR preparation.
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PMID:A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100). 258 62

We compared the chronic (2-year) effect of substitution with Sinemet CR with the effect of continued administration of standard Sinemet on motor fluctuations and drug-induced side effects in Parkinson's disease (PD). Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry. After 2 years, both groups were more disabled from their PD than at baseline; the disability scores were equivalent for the 2 treatments. The Sinemet CR group had fewer fluctuations and fewer side effects. Compared with the standard Sinemet group, Sinemet CR patients had more "on" time (mean 83% versus 62%, p less than 0.001), and had a lower prevalence of disabling chorea (p less than 0.007), dystonia (p less than 0.003) and sleep disruption (p less than 0.002). Prevalence of hallucinations was equivalent for the 2 groups. These results suggest that Sinemet CR is beneficial in ameliorating and preventing the high frequency of some side effects of standard Sinemet treatment.
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PMID:Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa. 258 64

Therapeutic responses to Sinemet CR were studied in 37 patients with early Parkinson's disease previously treated with standard (Madopar) or controlled-release (Madopar HBS) levodopa/benserazide combinations. Patients were followed up for a 3-month period. The optimal therapeutic response of parkinsonian disability to Sinemet CR was equal to that obtained with Madopar or Madopar HBS. The optimal therapeutic dosage of Sinemet CR was equal to that of Madopar HBS but 12% higher than that of standard Madopar. However, with Sinemet CR treatment, the number of daily doses needed was significantly fewer than with both previous treatments. End-of-dose failure, which had developed in 4 patients, and peak-dose dyskinesias present in 6 patients during treatment with standard Madopar, improved significantly with Sinemet CR. Thus, Sinemet CR seems to be beneficial and useful in the treatment of early Parkinson's disease.
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PMID:Treatment of early Parkinson's disease with controlled-release levodopa preparations. 258 66

The efficacy of controlled-release Sinemet was evaluated in a 52-week open trial involving 20 patients (14 men, 6 women; mean age 66 years, range 56 to 82) with idiopathic Parkinson's disease of 8 years' mean duration. The mean daily dosage of levodopa was 662.5 mg (200 to 1600 mg) on entering the study and 800 mg (200 to 2400 mg) after 52 weeks. The mean number of daily doses was reduced from 5.0 (2 to 16) at entry to 3.3 (1 to 6) after 52 weeks. Rigidity, tremor, and bradykinesia were scored at 3 intervals during baseline and 8 intervals during the study on controlled-release levodopa. All parameters improved, with maximum improvement seen at week 12. Side effects were less frequent on the controlled-release preparation. After 5 months, 1 patient developed protracted dyskinesia with freezing episodes and end-of-dose deterioration on dose frequency reduction.
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PMID:Sinemet CR in the treatment of patients with Parkinson's disease already on long-term treatment with levodopa. 258 67

Sinemet CR, a controlled-release form of carbidopa/levodopa, was administered for 36 or 39 months to 8 patients with Parkinson's disease in an open-label study. On standard Sinemet each patient had experienced "wearing off" phenomena, and 5 had also experienced random "off" episodes. Daily "on" time, dyskinesia time, disability score, levodopa dosage requirement, and dosing frequency on Sinemet CR were compared with baseline values on standard Sinemet therapy. After both 3 and 36 or 39 months of Sinemet CR therapy, 5 patients showed increased daily "on" time compared with baseline. All 8 required fewer daily doses after 3 months on Sinemet CR, but only 3 were still taking fewer doses after 36 or 39 months. Disability scores remained essentially unchanged. Patients continued to elect to remain on Sinemet CR over the 3-year period, citing improved predictability of response and less severe and precipitous "off" episodes as the main reasons. This experience suggests that patient acceptance of Sinemet CR remains high. A modest improvement in "on" time can be achieved and maintained in some patients for as long as 3 years. However, as with standard Sinemet, dosing frequency for Sinemet CR may need to be gradually increased with time in order to maintain benefits achieved.
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PMID:Long-term clinical efficacy of Sinemet CR in patients with Parkinson's disease. 258 69

Twelve of 23 patients with Parkinson's disease and motor fluctuations who entered a double-blind study comparing controlled-release carbidopa/levodopa (Sinemet CR-4) with standard Sinemet (SS) continued into open label follow-up on a combination of CR-4 and SS (C/S); the rest continued on CR-4 alone. Significant improvement on C/S compared with CR-4 was noted for shorter duration and reduced disability of dyskinesias, and more hours "on" without dyskinesias (all p less than 0.05). Total number of hours "off" was improved on C/S over SS (p less than 0.01). Sinemet CR-4 proved to be better than C/S for sleep disturbance (p less than 0.05). Although the total number of tablets and doses per day of CR-4 was reduced during the C/S period, total levodopa dosage per day was not significantly changed from either of the previous periods. The C/S therapy for advanced parkinsonism can be more efficacious for fluctuators than either CR-4 or SS alone.
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PMID:Controlled-release carbidopa-levodopa (Sinemet) in combination with standard Sinemet in advanced Parkinson's disease. 266 26

"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

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


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