PHARMACOKINETICS OF DIAZEPAM IN DISORDERED LIVER-FUNCTION

The plasma elimination curves of diazepam following i.v. administration of 10 mg were studied in 9 patients with cirrhosis of the liver and 4 patients without liver disease. The data were analyzed according to a 2-compartment model. The mean biological half-life (T/2) of diazepam was increased 5-fold in patients with cirrhosis compared to the controls (164 h vs. 32.1 h). The plasma clearance of diazepam could be correlated neither with a quantitative measure of liver function, as estimated by galactose elimination capacity, nor to semiquantitative measures of liver function, such as serum albumin and prothrombin. The plasma clearance of diazepam is probably an inaccurate index of its rate of hepatic metabolism due to the complex kinetics of the drug.