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.
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Received: 4 July 1997 Received in revised form: 24 October 1997 Accepted: 19 November 1997
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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
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DOI: https://doi.org/10.1007/s004150050209