Abstract
Article abstract –Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. In an open-label trial, we examined the effects of entacapone, a peripheral inhibitor of COMT, administered acutely or for 8 weeks, on the pharmacokinetics and pharmacodynamics of levodopa in 15 parkinsonian subjects with a fluctuating response to levodopa. Acutely and chronically administered entacapone similarly decreased the plasma elimination of orally and intravenously administered levodopa. Absorption of levodopa was minimally affected. During chronic entacapone treatment, daily levodopa dosages were reduced by 27% yet mean plasma levodopa concentrations were increased by 23%. Plasma 3-O-methyldopa concentrations were decreased by 60%. Entacapone increased the duration of action of single doses of levodopa by a mean of 56%. The percent of the day “on” after 8 weeks of entacapone treatment was 77%; it dropped to 44% upon withdrawal of entacapone. We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa.
- © 1994 by AAN Enterprises, Inc.
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