Induction of hexobarbital and antipyrine metabolism by rifampicin treatment in the pig

Abstract

The rates of antipyrine and hexobarbital elimination from blood or plasma were used to determine whether the antibiotic rifampicin is an inducer of microsomal oxidative drug metabolism in the pig. Treatment with rifampicin (300 mg, po, twice daily for 7 days) decreased hexobarbital and antipyrine elimination half-lives by 65 and 62%, respectively. This was associated with an increase of the metabolic clearance by 222% for hexobarbital and 255% for antipyrine. However, not in all pigs was an increase of antipyrine clearance observed. The antipyrine metabolite profile was determined before and after rifampicin treatment. The partial clearance of 4-hydroxyantipyrine, as measured on the basis of urinary excretion data, increased about fourfold. Neither norantipyrine nor 3-hydroxymethylantipyrine were detectable in urine before rifampicin treatment. Only after rifampicin treatment could a small amount of 3-hydroxymethylantipyrine be measured. It is concluded that rifampicin is a potent inducer of microsomal oxidative drug metabolism in the pig. In contrast to other animal species, the pig seems to represent a suitable animal model for further study of rifampicin induction. Because of the increase of hexobarbital clearance in all cases and lack of increase of antipyrine clearance in some pigs, a similarity between the situation in man and pig seems to exist.