Differential induction of antipyrine metabolism by rifampicin

Antipyrine is oxidised to three main metabolites in man. There is evidence that the different metabolites are products of different forms of cytochrome P-450. The effect of rifampicin administration for two weeks on the rates of formation of these metabolites was investigated in healthy volunteers. Rifampicin increased antipyrine clearance and shortened its half-life. Two weeks after stopping rifampicin the induction had largely been reversed. Clearance to all three metabolites was increased by rifampicin. Clearance to 3-hydroxymethylantipyrine was increased from 7.8 +/- 0.9 ml/min to 13.3 +/- 1.3 ml/min, to norphenazone from 5.8 +/- 0.6 ml/min to 19.3 +/- 2.1 ml/min and to 4-hydroxyantipyrine from 14.3 +/- 2.2 ml/min to 21.9 +/- 3.9 ml/min. Thus clearance to norphenazone was increased to a much greater extent than to either of the other two metabolites. It is concluded that this provides evidence for the involvement of at least two different forms of cytochrome P-450 in antipyrine metabolism in man.