Increased Glucuronidation of Bilirubin in Man and Rat by Administration of Antipyrine (Phenazone)

1. Antipyrine in a dose of 3·2 mmol (600 mg) daily for 6 weeks produced a significant fall in both total and unconjugated serum bilirubin concentrations in six patients with Gilbert's syndrome. The maximum reduction in serum bilirubin concentration was seen after 2 weeks of treatment.

2. In the rat, administration of antipyrine in doses of 0·42 and 1·27 mmol 24 h⁻¹ kg⁻¹ (80 and 240 mg 24 h⁻¹ kg⁻¹) for 84 h caused a significant increase in the apparent maximal velocity (V_max.) for the glucuronidation of bilirubin by liver microsomal preparations when the concentration of either uridine diphosphate glucuronic acid (UDPGA) or bilirubin was altered. There was no significant difference between the apparent V_max. values attained with the two doses of antipyrine in either set of experiments. Neither the microsomal protein content nor the apparent affinity constant (K_m) was altered in these studies.

3. In contrast, administration of phenobarbitone in doses of 0·34 mmol 24 h⁻¹ kg⁻¹ (80 mg 24 h⁻¹ kg⁻¹) caused a significant increase in the microsomal protein content but there was no significant change in the values for the apparent V_max. or apparent K_m for the glucuronidation of bilirubin with various concentrations of both UDPGA and bilirubin.