Enzyme-inducing Drug Combinations and Their Effects on Liver Microsomal Enzyme Activity in Man

The effect of 2 different drug combinations on liver microsomal activity was investigated in healthy volunteers by administering antipyrine 1200 mg and phenobarbitone 100 mg, or the same dose of antipyrine with rifampicin 600 mg daily for 14 days. The effect of rifampicin 1200 mg given for only 8 days was also studied. Before and after each drug regimen, estimates were made of the total body clearance of antipyrine, gamma-glutamyl-transferase (gamma-GT) and urinary excretion of 6-beta-hydroxycortisol as in vivo parameters of liver microsomal enzyme activity. Following combined antipyrine and phenobarbitone administration, the antipyrine clearance was increased by 80%, after antipyrine with rifampicin by 128%, and after rifampicin alone by 104%. 6-beta-hydroxycortisol, corrected for 17-hydroxycorticosteroids, increased from 2.6% to 8% following antipyrine plus phenobarbitone, from 4.4% to 27.9% following antipyrine plus rifampicin, and from 5.4% to 29.7% after rifampicin given alone. Based on previous studies, antipyrine given with phenobarbitone produced slightly more induction than phenobarbitone given alone. Following antipyrine 1200 mg with rifampicin 600 mg for 14 days a significantly greater increase in antipyrine clearance and 6-beta-hydroxycortisol excretion was observed than when either drug was given alone.