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Departments of Neurology, School of Medicine (Drs. Nutt, Woodward, Gancher, and Hammerstad and R.M. Beckner, C.K. Stone, K. Berggren, and J.H. Carter)
Departments of Pharmacology (Dr. Nutt)
Departments of Biochemistry and Molecular Biology, School of Medicine (Dr. Woodward, R.M. Beckner, and K. Berggren)
Department of Adult Health and Illness, School of Nursing, Oregon Health Sciences University, Portland, (J.H. Carter)
Department of Orion-Farmos Pharmaceuticals Research Center, Espoo, Finland. (Dr. Gordin)
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.
Address correspondence and reprint requests to Dr. J.G. Nutt, Department of Neurology, L-226, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098.
Supported in part by NIH grants NS21062 and RR00334 and a grant from Orion-Farmos Pharmaceuticals.
Received July 27, 1993. Accepted for publication in final form November 1, 1993.
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