The effect of Madopar (benserazide and L-dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-L-methionine by Madopar would change the disposition of tolcapone. There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.
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Toxicol In Vitro
August 2016
KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim, France; Université de Franche-Comté, EA4267, 25030 Besançon, France. Electronic address:
J Pharmacokinet Pharmacodyn
April 2006
Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, M13 9PL, UK.
We address the problem of designing pharmacokinetic experiments in multivariate response situations. Criteria, based on the Fisher information matrix, whose inverse according to the Rao-Cramer inequality is the lower bound of the variance-covariance matrix of any unbiased estimator of the parameters, have previously been developed for univariate response for an individual and a population. We extend these criteria to design individual and population studies where more than one response is measured, for example, when both parent drug and metabolites are measured in plasma, multi-compartment models, where measurements are taken at more than one site, or when drug concentration and pharmacodynamic data are collected simultaneously.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
October 1999
The Subfemtomole Biorecognition Project, Uppsala University and Japanese Research and Development Council, Sweden.
11C-labeled 3,4-Dihydroxy-phenyl-L-alanine (L-DOPA) and L-fluorodopa were used as tracers for the functional state of the presynaptic dopamine system in anesthetized monkeys with positron emission tomography. The radiotracer disposition in brain tissue and plasma were studied and effects induced by pharmacologic challenges were evaluated. 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) increased the striatal influx rate constant, e.
View Article and Find Full Text PDFPharmacotherapy
January 1999
College of Pharmacy, University of Minnesota, Minneapolis, USA.
Tolcapone is a selective peripheral and central catechol-O-methyltransferase (COMT) inhibitor recently approved as adjunctive therapy in patients with idiopathic Parkinson's disease who are already being treated with a levodopa-peripheral dopa decarboxylase inhibitor (DDI) combination. Tolcapone potentiates and prolongs the effect of levodopa in the central nervous system (CNS) by enhancing levodopa's delivery to the CNS and slowing dopamine's central metabolism. A short terminal disposition half-life of 2 hours mandates dosing 3 times/day.
View Article and Find Full Text PDFNeuroreport
March 1997
Equipe NeuroPsychoPharmacologie Université d'Auvergne, Laboratoires de Pharmacologie, Faculté de Pharmacie, Clermont-Ferrand, France.
The influence of tolcapone, an inhibitor of catechol-O-methyl transferase, was evaluated on the disposition of apomorphine, a dopamine agonist used to treat Parkinson's disease, to explain a previously observed increase of duration of the effect of apomorphine associated with tolcapone. Sampling was performed in rats before and at different times after administration of apomorphine and following that of tolcapone or saline. Both in plasma and striatum, times to reach maximal-concentration and maximal concentrations did not significantly differ between the two groups but the elimination half-life times and areas under the curve were significantly greater following tolcapone treatment than in the saline group.
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