Differences in Hepatic Drug Metabolism in Various Rabbit Strains Before and After Pretreatment with Phenobarbital.

Abstract

Summary The results of these experiments indicate that basal levels of activity of hepatic microsomal drug metabolizing enzyme systems from various rabbit strains can vary as much as 20-fold in the strains studied. This is particularly true of hexobarbital, amphetamine, and aminopyrine metabolism where the widest variations were observed. Relatively little strain variation was seen in the basal metabolism of chlorpromazine. The wild rabbits and California rabbits exhibited the greatest differences from other rabbit strains in basal hepatic drug metabolism. A wide range of variability was also observed in the response of hepatic drug metabolizing enzyme systems to in vivo pre-treatment with phenobarbital. Especially noteworthy were the 26-fold increase in hexobarbital metabolism seen with the hepatic enzyme systems of Cottontails, the 7.5-fold increase in metabolism of p-nitrobenzoic acid in Jack rabbits, and the significant increases in 3,4-benzpyrene metabolism observed only in the wild rabbits. Also interesting was the lack of phenobarbital stimulation of p-nitrobenzoic acid and zoxazolamine metabolizing systems in California rabbits. Jack rabbits, Cottontails, and California rabbits again exhibited the widest deviations from the general pattern, whereas Dutch, English, and New Zealand strains showed fair agreement among themselves in response to phenobarbital treatment.