title: Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency.
abstract: The pharmacokinetics of pyrazinamide (Pirilène) and its metabolites are evaluated in ten subjects with hepatic insufficiency, after an oral dose of 19.3 +/- 0.6 mg.kg-1 and the results are compared to those of a group of nine healthy subjects (control group). The results exhibit a marked reduction of the pyrazinamide total clearance (0.48 vs 0.84 ml.min-1.kg-1) and an increase in half-life from 9.19 h to 15.07 h in the patients group. The area under the curve of pyrazinoic acid (the main metabolite) is increased from 97 to 280 mg.h.l-1 with a half-life twice as much as that of the control group. The hepatic insufficiency entails a marked reduction of the common posology as well as a closer survey of the biologic hepatic parameters and of uric acid the renal elimination of which is inhibited by pyrazinoic acid.
authors.affiliation: Unité de Pharmacocinétique, Centre Hospitalier Général, Le Havre, France.
authors.forename: C
authors.initials: C
authors.lastname: Lacroix
authors.forename: J L
authors.initials: JL
authors.lastname: Tranvouez
authors.forename: T
authors.initials: T
authors.lastname: Phan Hoang
authors.forename: H
authors.initials: H
authors.lastname: Duwoos
authors.forename: O
authors.initials: O
authors.lastname: Lafont
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: C032191:5-hydroxypyrazinamide; D011718:Pyrazinamide; C005296:pyrazinoic acid; C054996:5-hydroxypyrazinoic acid