Effect of liver impairment on the pharmacokinetics of tolcapone and its metabolites

Clinical Pharmacology and Therapeutics
K M JorgaJ van Hattum

Abstract

To assess the effect of liver impairment on the pharmacokinetics of tolcapone and to derive appropriate dose recommendations for patients with this disease who are undergoing treatment for Parkinson's disease. In an open, two-way crossover study, 16 patients with moderate liver disease (eight with cirrhotic and eight with noncirrhotic liver disease) and eight healthy subjects received an oral dose of 200 mg tolcapone and an intravenous dose of 50 mg tolcapone on separate occasions. The concentrations of total and unbound tolcapone and its three major metabolites (tolcapone glucuronide, carboxylic acid, and 3-O-methyl metabolite) were assessed in plasma and urine. On the basis of total drug concentration, the differences in tolcapone pharmacokinetics between the groups were small. However, lower clearance and volume of distribution of unbound drug were found among patients with cirrhosis than among control subjects. Plasma concentration of the pharmacologically inactive glucuronide metabolite was increased among patients with cirrhosis. Half of the recommended dosage of tolcapone should be administered to patients with cirrhosis of the liver to maintain the target steady-state concentration of unbound drug and to avoid accumulat...Continue Reading

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Citations

Dec 22, 1999·British Journal of Clinical Pharmacology·K JorgaJ L Steimer
Dec 1, 2007·Clinical Interventions in Aging·Fabrizio Stocchi, Maria Francesca De Pandis
Apr 10, 2013·Expert Opinion on Drug Metabolism & Toxicology·José A G AgúndezFélix Javier Jiménez-Jiménez
May 10, 2012·Expert Opinion on Drug Metabolism & Toxicology·Yin Cheong WongZhong Zuo
Oct 25, 2006·Expert Opinion on Pharmacotherapy·Julie Leegwater-Kim, Cheryl Waters
Jul 5, 2005·Expert Opinion on Investigational Drugs·T A Zesiewicz, R A Hauser
Dec 7, 2007·Expert Review of Neurotherapeutics·Julie Leegwater-Kim, Cheryl Waters
Mar 22, 2006·Journal of Pharmacokinetics and Pharmacodynamics·Ivelina GueorguievaMalcolm Rowland
May 12, 2000·Journal of Clinical Pharmacology·K M JorgaH Birnboeck
Jun 18, 2009·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Chantal SchlatterStephan Krähenbühl
Dec 3, 1999·British Journal of Clinical Pharmacology·K JorgaR Gasser

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