Use of Liver Function Tests as Predictors of Rifampicin Metabolism in Cirrhosis

Abstract

Normal subjects taking rifampicin regularly, show a fall in serum and urinary drug concentrations from enzyme induction and increased biliary excretion. In cirrhosis, hepatocellular dysfunction and impaired biliary excretion may prevent these changes, but there is little information on how the drug should be prescribed in such patients. Serum and urinary rifampicin concentrations were therefore measured in thirteen patients and five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower than on Day 1 (7.0 +/- 3.0 and 8.0 +/- 1.0 microgram/ml respectively) and this was also the case for nine cirrhotic patients with mild impairment of liver function (6.0 +/- 1.0 and 11.0 +/- 2.0 microgram/ml (p less than 0.02). In both groups there was an accompanying fall in urinary rifampicin excretion due to a decrease in desacetylrifampicin excretion. In the remaining four cirrhotic patients, peak serum rifampicin levels rose from 11.0 +/- 5.0 to 17.0 +/- 6.0 microgram/ml and urinary excretion of desacetylrifampicin did not fall. Although values for serum albumin and prothrombin time were of limited value in predicting drug accumulation, pretreatment levels of bilirubin exceeding 50 mumol/l were present in all four patients showing an increase in serum rifampicin concentration. Furthermore, only in this group was there a rise in serum bilirubin during treatment, almost certainly the result of competition between rifampicin and bilirubin for hepatic uptake and excretion. In all patients with cirrhosis, bilirubin concentrations exceeding 50 mumol/l should be an indication for reduction of rifampicin dosage.