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

Arzneimittelforschung. 1990 Jan;40(1):76-9.

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.

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Female
  • Half-Life
  • Humans
  • Liver Cirrhosis / metabolism*
  • Liver Function Tests
  • Male
  • Pyrazinamide / analogs & derivatives
  • Pyrazinamide / blood
  • Pyrazinamide / metabolism
  • Pyrazinamide / pharmacokinetics*

Substances

  • 5-hydroxypyrazinamide
  • Pyrazinamide
  • pyrazinoic acid
  • 5-hydroxypyrazinoic acid