title: Disposition of hexobarbital in intra- and extrahepatic cholestasis in man and the influence of drug metabolism-inducing agents.
abstract: The pharmacokinetics of intravenously infused hexobarbital was studied in 10 patients with intrahepatic cholestasis and in 9 with extrahepatic biliary obstruction. The results were compared with those obtained in 16 healthy young volunteers and 5 older patients with normal liver function. After infusion, the plasma concentrations showed a rapid initial decline (alpha-phase) and subsequently a slower decrease (beta-phase). The half-life of a latter phase was 323 +/- 84 min in the healthy group, 357 +/- 151 min in the patients with intrahepatic cholestasis and 344 +/- 115 min in the group with biliary obstruction; the clearances were 3.41 +/- 0.90, 4.08 +/- 1.95 and 3.81 +/- 1.97 ml x min-1 x kg-1, respectively. The differences were not statistically significant. The mean volume of the central compartment of distribution and the steady state volume of distribution were not significantly different. In two patients hexobarbital clearance during cholestasis was greater than after it had subsided. After treatment of 11 patients with cholestasis with drug metabolism-inducing agents (phenobarbital, rifampicin or phenytoin), the half-life of hexobarbital was significantly shortened and the mean value of hexobarbital clearance was more than doubled.
mesh_terms: D000328:Adult; D000368:Aged; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D002780:Cholestasis, Intrahepatic / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D006591:Hexobarbital / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D007700:Kinetics; D008099:Liver / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology
chemical_list: D010672:Phenytoin; D006591:Hexobarbital; D012293:Rifampin; D010634:Phenobarbital