Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage. After a 1-week placebo run-in, 97 patients were assigned randomly to receive placebo or tolcapone 200 or 400 mg three times daily (t.i.d.). Levodopa dosage was reduced by -35% on day 1 of study and subsequently retitrated as required. After 6 weeks, the tolcapone groups crossed over to receive the other dose for a further 3 weeks for exploratory purposes. Both tolcapone groups had greater reductions in levodopa dosage than the placebo group at week 6 (not statistically different). The 200-mg t.i.d. group showed greatest improvement in estimated mean scores for all efficacy parameters (p < 0.05 versus placebo for change in Unified Parkinson's Disease Rating Scale Subscale II). Fewer dopaminergic and nondopaminergic adverse events were associated with tolcapone 200 mg t.i.d. than with tolcapone 400 mg t.i.d. The most frequently reported dopaminergic adverse events were nausea, cramps, dyskinesia, and dystonia. The most frequently reported unanticipated adverse event was diarrhea. Tolcapone 200 mg t.i.d. may provide additional benefit to patients with moderately advanced Parkinson's disease with treated "wearing-off" phenomenon.
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PMID:Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson's Disease Study Group II (TIPS II). 939 17

The catechol-O-methyltransferase inhibitor tolcapone was compared with the dopamine agonist bromocriptine in an open-label, randomized trial involving 146 levodopa-treated parkinsonian patients with end-of-dose deterioration of efficacy. Tolcapone was given at a dosage of 200 mg three times daily; bromocriptine was titrated from 1.25 mg once daily at baseline to, at most, 10 mg three times daily by day 24 (mean final dose 22.4 mg/day). After 8 weeks, the tolcapone group had a significant reduction in daily levodopa dose compared with the bromocriptine group (p<0.05). No significant differences in the "on/off" time and motor disability were seen between the tolcapone and bromocriptine treatment groups. Bromocriptine induced more hallucinations, orthostatic hypotension, and nausea, whereas tolcapone therapy was associated with more muscle cramps and dystonia. These results suggest that when added to levodopa therapy, the two drugs have a different side effect profile, with the advantages for tolcapone being absence of titration and quicker efficacy.
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PMID:Efficacy and tolerability of tolcapone compared with bromocriptine in levodopa-treated parkinsonian patients. Tolcapone Study Group. 991 42

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of tolcapone are reviewed. Tolcapone is the first drug brought to market from the new class of selective and reversible inhibitors of catechol-O-methyltransferase. Tolcapone is indicated for use in the treatment of Parkinson's disease as an adjunct to levodopa-carbidopa therapy in patients who are experiencing fluctuations in symptoms and who are not responding to or are not appropriate candidates for other adjunctive therapies. The absolute bioavailability of tolcapone after an oral dose is about 65%. Clinical trials have demonstrated that tolcapone 50-200 mg three times daily reduces "off" time in patients refractory to levodopa-carbidopa, Unified Parkinson's Disease Rating Scale scores, and the dosage of levodopa-carbidopa required for symptom suppression. The most frequent adverse effects of tolcapone are dyskinesia, nausea, sleep disorders, dystonia, orthostatic hypotension, diarrhea, dizziness, and hallucinations; also, there is a potential for elevation of liver transaminase concentrations in the blood. To date, three deaths from fulminant hepatic failure in association with tolcapone have been reported. Extensive liver function testing is required of all patients before and during therapy. The recommended starting dosage is 100 mg orally three times daily as an adjunct to levodopacarbidopa therapy; a concurrent reduction in the levodopa dosage of about 30% is suggested. Patient response should be monitored carefully during the first three weeks of therapy; treatment should be discontinued in patients failing to respond during this initial use. Tolcapone is of benefit in fluctuating Parkinson's disease, but benefits must be carefully weighed against risks in individual patients.
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PMID:Tolcapone: a novel approach to Parkinson's disease. 1056 98