Hepatic Drug Metabolism in Ten Strains of Norway Rat Before and After Pretreatment with Phenobarbital

Summary

Two- to three-fold differences in the metabolism of ethylmorphine and aniline have been described in the 9000g liver supernatant from 10 strains of Norway rat. In the 9000g supernatant wild Norway rats resembled domestic Norway rats in ethylmorphine and aniline metabolism, but in the microsomal fraction wild rats had lower V _max for ethylmorphone N-demethylase and higher apparent K _m than 10 domestic strains. In accordance with this observation, the P-450 values of the hepatic microsomal fraction were approximately 1.0 mμmoles for 10 domestic strains of the Norway rat and 0.5 mμmoles for the wild Norway rat. Greater variability of wild rats both for P-450 and apparent K _m for ethylmorphine N-demethy-lase suggests exposure of individual animals to different amounts of inducing agents. Male Norway rats metabolized ethylmorphine 50 to 300% more rapidly than did females, but in only three strains were similar sex differences observed for aniline. Conversely, in the distinct species Dipodomys merriam (kangaroo rats), females metabolized both drugs more rapidly than did males. In 10 strains of domestic rat, phenobarbital pretreatment elevated ethylmorphine metabolism 2.0- to 3.8-fold; aniline metabolism increased 1.5- to 3.5-fold. Implications of decreased hepatic microsomal drug-metabolizing activity in wild compared to domestic animals of the same species are discussed.