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2826272 
Technical Report 
Drug metabolism and therapeutics 
Conney, AH 
1969 
HAPAB/70/00104 
J 
12 
653-60 
HAPAB The variables that influence hepatic drug metabolism as well as some of the effects of altered metabolism are emphasized in this survey of the metabolic effects of medications and the possible effects of one drug on the metabolism of another. The areas covered include metabolites with biologic activity, impaired drug metabolism in neonates and individual variations in drug metabolism. Pesticides are included in the discussions of the inhibition and stimulation of drug metabolism and the stimulatory effects of drugs on the metabolism of normal body constituents. SKF 525-A (beta-diethyl-amino- ethyldiphenylpropylacetate has been found to produce as much as a fivefold inhibition of hexobarbital and phenylbutazone metabolism by liver microsomal enzymes experimentally in rodents and dogs. Chemicals found in the environment, such as DDT, chlordane and 3,4-benzyprene, have been found to stimulate drug metabolism by enzyme induction. Both in vitro and in vivo experiments have shown that liver microsomal metabolism of bishydroxycoumarin is increased significantly by prior or simultaneous administration of phenobarbital. A number of structurally unrelated drugs and insecticides which stimulate drug-metabolizing enzymatic activity have been found also to stimulate steroid hydroxylase activity; these compounds include chlordane, DDT and o'p'- DDD. o,p'-DDD markedly stimulates cortisol metabolism to the minor metabolite, 6beta-hydroxycortisol, in rats. o,p'-DDD's stimulatory effect on cortisol metabolism to highly polar urinary 17- hydroxycorticoid metabolites which are poorly extractable into chloroform rather than, as previously thought that it decreases urinary 17-hydroxycorticoids by direct action on the adrenal glands. It is clear that many drugs affect hepatic enzyme systems, thus altering both normal metabolism and the metabolism of concurrently administered drugs substantially. It is essential to define the nature and importance of these interactions accurately. Measurement of plasma drug levels would aid the clinician in achieving effective therapy without toxicity. It is important that routine methods for the rapid analysis of drug levels in a drop of blood be developed. TOXICOLOGY AND PHARMACOLOGY 70/01/00, 28 1969