Effect of enzyme induction on plasma lipids using antipyrine, phenobarbital, and rifampicin.

Abstract

The liver microsomal enzyme system was induced by antipyrine, phenobarbital, or rifampicin in 19 healthy subjects and the effect on plasma lipids was followed. Before and after each study antipyrine elimination, γ‐glutamyl‐transpeptidase, D‐glucaric acid, and 6‐β‐hydroxycortisol were measured, and plasma lipids including lipoprotein electrophoresis were estimated. The subjects were given 1,200 mg antipyrine, 100 mg phenobarbital, 600 mg rifampicin, or 1,200 mg rifampicin daily for 14 days. Following enzyme induction by antipyrine, the antipyrine half‐life fell from 11.8 to 8.7 hr, by phenobarbital, from 13.8 to 8.9 hr, by rifampicin (600 mg), from 11.7 to 7.1 hr, and by rifampicin (1,200 mg), from 11.7 to 5.6 hr; the antipyrine clearance was increased after antipyrine by 30%, after phenobarbital, by 56%, after rifampicin (600 mg), by 59%, and after rifampicin (1,200 mg), by 125%. D‐Glucaric acid excretion in urine showed a tendency to rise to the same extent in each group, while the γ‐glutamyl‐transpeptidase values were affected similarly after antipyrine and phenobarbital but remained unchanged after rifampicin. The 6‐β‐hydroxycortisol urinary excretion corrected by the 17‐hydroxycorticosteroids increased in all groups. There were no changes in plasma cholesterol, triglyceride, and other plasma lipids measured, and lipid electrophoresis was unchanged. Steady‐state plasma concentrations of cholesterol and plasma triglycerides were not elevated after induction of the microsomal enzyme system by the drugs used.