Genetics of drug transformation.

Biotransformations of drugs are controlled or strongly affected by genetic factors. During the past few years several genetic deficiencies of drug-metabolizing reactions catalyzed by members of the family of cytochrome P-450 were observed. Choice of the appropriate drug to study and attention to urinary metabolites have been the essential ingredients for the recent discovery of genetic deficiencies of drug metabolism in man which include recessive deficiency of debrisoquine/sparteine metabolism and of mephenytoin metabolism. The clinical significance of these defects is discussed. Ethanol after metabolism to acetaldehyde is further metabolized to acetic acid by aldehyde dehydrogenase. Numerous isozymes of aldehyde dehydrogenase exist, one of which possesses a high affinity for acetaldehyde. Approximately 40% of the Oriental population lack this high affinity isozyme so that in these individuals who may have symptoms of flushing and other unpleasant effects the acetaldehyde formed is destroyed only at high plasma concentrations.