Skip to main content
Log in

The effect of tolcapone on levodopa pharmacokinetics is independent of levodopa/carbidopa formulation

  • Original communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Clinical pharmacology studies have shown that the catechol-O-methyltransferase inhibitor tolcapone increases the bioavailability area under the plasma concentration-time curve (AUC) and the plasma elimination half-life (t 1/2) of levodopa. The objective of the study was to evaluate the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after coadministration of tolcapone 200 mg with levodopa/carbidopa in the following doses: 100/10 mg, 100/25 mg, 200/20 mg, 200/50 mg, 250/25 mg (all immediate-release) and 200/50 mg (controlled-release). Thirty healthy male volunteers were divided into four groups: three groups of 8 and one group of 6. Participants in the first three groups received two formulations of levodopa/carbidopa. Each dose was administered on two occasions, once with tolcapone 200 mg andonce with placebo (four-way crossover). In the fourth group, one formulation was given on two occasions, once with tolcapone 200 mg and oncewith placebo (two-way crossover). Dosing days were separated by a 7-day washout. The effect of tolcapone on levodopa and 3-OMD pharmacokinetics was found to be similar with all levodopa/carbidopa formulations. The absorption of levodopa wasunaffected by tolcapone in all treatment groups and the maximum plasma concentration (C max ) remained unchanged. When tolcapone was given with the immediate-release formulations, levodopa AUC increased by 60–90% and levodopa t 1/2 by 20–60%. With tolcapone and the controlled-release formulation, AUC increased by 80% and t 1/2 by 60%. With all levodopa/carbidopa formulations, 3-OMD C max decreased by 80% and AUC by 70% with tolcapone. Thetolerability of all treatment combinations was similar. We conclude that adjunctive treatment with tolcapone should have similar levodopa-potentiating clinical effects, regardless of the levodopa/carbidopa formulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Received: 4 July 1997 Received in revised form: 24 October 1997 Accepted: 19 November 1997

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jorga, K., Fotteler, B., Sedek, G. et al. The effect of tolcapone on levodopa pharmacokinetics is independent of levodopa/carbidopa formulation. J Neurol 245, 223–230 (1998). https://doi.org/10.1007/s004150050209

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s004150050209

Navigation