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Entacapone improves the availability of l-dopa in plasma by decreasing its peripheral metabolism independent of l-dopa/carbidopa dose.
- Source :
-
British Journal of Clinical Pharmacology . Oct2002, Vol. 54 Issue 4, p363-371. 9p. - Publication Year :
- 2002
-
Abstract
- Aims Entacapone is a peripherally acting catechol-O-methyltransferase (COMT) inhibitor. To improve the benefits of oral l-dopa in the treatment of Parkinson's disease (PD), entacapone is administered as a 200 mg dose with each daily dose of l-dopa. This study evaluated the effects of entacapone 200 mg on the pharmacokinetics and metabolism of l-dopa given as standard release l-dopa/carbidopa. Methods Six different doses of l-dopa/carbidopa were investigated in this placebo-controlled, double-blind (regarding entacapone), randomized, single-dose study in 46 young healthy males. The subjects were divided into three groups (n = 14–16). Two different l-dopa/carbidopa doses were administered to each subject (50/12.5 mg and 150/37.5 mg, or 100/10 mg and 100/25 mg, or 200/50 mg and 250/25 mg). Each dose was given on two occasions; simultaneously with entacapone or with placebo, in random order, on two consecutive study visits, separated by a washout period of at least 3 weeks (four-way crossover design). Serial blood samples were drawn before dosing and up to 24 h after the dose and pharmacokinetic parameters of l-dopa, its metabolites, carbidopa, and entacapone were determined. Results Entacapone increased the AUC(0,12 h) of l-dopa to a similar extent at all doses of l-dopa/carbidopa, that is by about 30–40% compared with placebo (P < 0.001, 95% CI 0.15, 0.40). When evaluated as the ratio of geometric means, entacapone slightly decreased the mean C max values for l-dopa at all l-dopa/carbidopa doses compared with placebo. When given with entacapone, higher plasma concentrations of l-dopa were maintained for a longer period at all doses of l-dopa/carbidopa. Entacapone also decreased the peripheral formation of 3-O-methyldopa (3-OMD) to about 55–60% of the placebo treatment level (P < 0.001, 95% CI -0.72, -0.35) and increased the mean AUC(0,12 h) of 3,4-dihydroxy-phenylacetic acid (DOPAC) 2–2.6-fold compared with placebo (P <... [ABSTRACT FROM AUTHOR]
- Subjects :
- *ENTACAPONE
*DOPA
*PHARMACOKINETICS
Subjects
Details
- Language :
- English
- ISSN :
- 03065251
- Volume :
- 54
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- British Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7606253
- Full Text :
- https://doi.org/10.1046/j.1365-2125.2002.01654.x