INFLUENCE OF AGE, SEX AND DRUG TREATMENT ON MICROSOMAL DRUG METABOLISM IN 4 RAT STRAINS

The present study describes the influence of sex, age and drug pretreatment on drug metabolism in four common strains of rats. Basal levels of activity of hepatic microsomal drug-metabolizing enzymes in the four strains varied considerably less than those reported in different rabbit and mouse strains. There was, in general, only a 2-fold variation in metabolic rate for a single drug. Young male and female Holtzman rats showed the lowest microsomal metabolism in all drug pathways examined. Phenobarbital pretreatment caused a stimulation of drug metabolism in young and adult, male and female rats of all strains. 3-Methylcholanthrene, on the other hand, often caused no change or decreased the rate. Evidence is presented which suggests that liver microsomes may contain a number of NADPH-dependent enzymes which differ in their rates of postpubertal development. © 1969.