Effect of drugs which alter microsomal drug-metabolizing enzyme activity on rat hepatic cholesterol biosynthesis

Effects on cholesterol biosynthesis of compounds known to alter hepatic microsomal drug metabolism were assessed in rats in vivo by measuring the simultaneous incorporation of tracer quantities of [1- 14C]acetate and 3H 2O into cholesterol. The incorporation of both substrates was increased with phenobarbital and decreased with CoCl 2 treatment. No change in incorporation of either substrate was noted when rats were treated with metyrapone, piperonyl butoxide or pregnenolone-16α-carboni-trile (PCN). The effect of these compounds on the assessment in vivo of cholesterol biosynthesis may be accurately characterized by use of either precursor as substrate. Compounds which induce or inhibit rat hepatic microsomal drug metabolism do not necessarily alter hepatic cholesterol biosynthesis.