Drugs and the liver—I: Effects of glutethimide and phenobarbital on hepatic bilirubin clearance, plasma bilirubin turnover and carbon monoxide production in man

Abstract

The effects of glutethimide and phenobarbital on the plasma unconjugated bilirubin concentration, hepatic bilirubin clearance (C BR) and plasma bilirubin turnover (BRT) were determined in 19 patients with mild chronic unconjugated hyperbilirubinemia (Gilbert's syndrome) and 11 normal volunteers. C BR and BRT were calculated from plasma radio-bilirubin disappearance curves obtained both before and during drug administration. The response to both drugs was essentially identical. During drug administration, the patients with Gilbert's syndrome attained a new steady state in which the plasma unconjugated bilirubin concentration ( BR) was 30 ± 2% ( mean ± S.E.M. ) and C BR 314 ± 25% of baseline. In the normal volunteers, BR fell to 65 ± 6%, while C BR increased to 135 ± 9% of baseline during the period of drug administration. Although neither total red cell volume nor the half-life of 51Cr-labeled erythrocytes was altered by either agent, daily plasma bilirubin turnover fell significantly (P < 0.05) to 87 ± 4% of baseline in the 30 subjects studied, and endogenous carbon monoxide production, which provides an independent estimate of the rate of heme degradation and bilirubin formation, was 93 ± 5 % of control (0.2 > P > 0.1). These studies indicate that both accelerated hepatic bilirubin clearance and reduced plasma bilirubin turnover contribute to the reduction in bilirubin concentration observed during administration of phenobarbital and glutethimide. The methods employed provided no evidence that these agents produce an increase in the rates of heme catabolism, bilirubin production or carbon monoxide formation.