Hexobarbital disposition in compensated and decompensated cirrhosis of the liver

Abstract

Hexobarbital disposition after intravenous infusion in 8 patients with compensated and 22 patients with decompensated liver cirrhosis was compared with that in 17 young healthy and 5 elderly subjects with normal liver function. The postinfusion plasma concentrations showed a rapid initial decay (a‐phase) and subsequently a slower decrease (β‐phase). The half‐life of this phase was 340 ± 110 min for the healthy volunteers, 509 ± 174 min for the patients with compensated liver cirrhosis, and 1,017 ± 450 min for the decompensated group. Clearance values were 3.32 ± 0.99, 1.88 ± 0.70, and 1.26 ± 0.49 ml · min −1 · kg −1 , respectively. The mean value for the steady‐state volume of distribution in decompensated cirrhosis appeared larger than in compensated cirrhosis and healthy volunteers, whereas the central compartment volume was reduced in compensated cirrhosis. The binding of 3 H‐hexobarbital by plasma proteins in cirrhotic patients and healthy controls did not differ. In one patient hexobarbital concentrations were also measured in ascites, which appeared to be identical to those in plasma after a relatively slow equilibrium period. In patients hexobarbital clearance appeared to be correlated with serum albumin concentration. For the patients with decompensated liver cirrhosis serum albumin has some predictive value with respect to drug clearance, whereas compensated liver cirrhosis is generally associated with normal or near normal albumin concentration despite reduced hexobarbital clearance.