Pharmacogenetic approaches to the prediction of drug response

The following review of pharmacogenetic progress and methodology is offered to stimulate and suggest analogous studies on drugs of abuse. It is readily acknowledged that formidable methodological problems are posed by adapting to drugs of abuse these pharmacogenetic approaches based on the administration of single safe doses of various prescription drugs to normal subjects under carefully controlled environmental conditions. Results of similarly designed studies on drugs of abuse in addicts might be uninterpretable because of confounding by numerous environmental perturbations, including the smoking of cigarettes and/or marijuana, nutritional variations, and intake of other drugs such as ethanol. Ethical considerations render objectionable the administration to unaddicted subjects of drugs at dosage levels usually ingested by drug abusers. Other approaches would have to be taken in such normal subjects. Possibilities include administration of tracer doses of /sup 14/C- or /sup 13/C- labeled drugs or growth of normal cells in culture to investigate their pharmacokinetic and/or pharmacodynamic responses to various drugs of abuse