PHARMACOKINETICS OF A SINGLE ORAL DOSE OF CLOBAZAM IN PATIENTS WITH LIVER-DISEASE

The pharmacokinetic effect of a single oral in dose of 20 mg clobazam was studied in 15 patients with liver disease and in 6 healthy volunte ers. Plasma concentrations of clobazam and its main metabolite, norclo bazam, were measured by gas liquid chromatography. Clobazam was rapidl y absorbed. Peak plasma concentrations were 350 +/- 63 ng/ml at 1.7 +/ - 0.8 hr in healthy volunteers, 239 +/- 70 ng/ml at 3 +/- 1.9 hr in pa tients with viral hepatitis and 240 +/- 113 ng/ml at 2.5 +/- 1.5 hr in patients with cirrhosis. Total distribution volume was 173 +/- 88 l a nd 168 +/- 71 l in patients with viral hepatitis and cirrhosis respect ively, and 81 +/- 20 l in volunteers. Corresponding half-life values w ere 47 +/- 18 hr and 51 +/- 21 hr in patients and 22 +/- 6.3 hr in vol unteers. The difference between patients was not significant, whereas the differrence between patients and volunteers was significant.