Pharmacokinetics, pharmacodynamics, and tolerability of tolcapone: a review of early studies in volunteers.

Abstract:

:Tolcapone is a potent, reversible inhibitor of catechol O-methyltransferase (COMT) intended for use as an adjunct to levodopa therapy for Parkinson's disease (PD). Findings from the first pharmacokinetics/pharmacodynamics and tolerability studies of tolcapone in volunteers are reviewed. Following linear and dose-proportional pharmacokinetics, tolcapone is rapidly absorbed and eliminated after single- or multiple-dose (i.e., tid) administration. Onset of COMT inhibition is rapid, substantial, and reversible, and is not affected by the co-administration of levodopa/decarboxylase inhibitor (levodopa/DCI). When given together with levodopa/DCI, tolcapone increases the relative bioavailability and plasma elimination half-life of levodopa, without affecting its peak plasma concentration. This leads to more stable plasma levels of levodopa, and the formation of 3-O-methyldopa is effectively reduced. Tolcapone was well tolerated alone or in combination with levodopa/DCI, and the results indicated that the effective dose in patients with PD would be in the range of 50-400 mg tid.

journal_name

Neurology

journal_title

Neurology

authors

Jorga KM

doi

10.1212/wnl.50.5_suppl_5.s31

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

S31-8

issue

5 Suppl 5

eissn

0028-3878

issn

1526-632X

journal_volume

50

pub_type

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