Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency.

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.