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March 9, 1970

Application of Metabolic Data to the Evaluation of Drugs

Author Affiliations

Kansas City, Kan

JAMA. 1970;211(10):1691. doi:10.1001/jama.1970.03170100053013

Five percent of hospital admissions is the consequence of adverse drug reactions. Many are preventable and related, in some manner, to the metabolism of the drug (induction or inhibition of drug metabolizing enzymes, pharmacogenetic abnormalities in the patient, poorly developed enzyme activities in infants). It is no longer possible to prescribe drugs rationally on the basis of a memorized schedule of dosages and contraindications since the same dose administered to different individuals or the same individual at different times may achieve a therapeutic, a toxic, or an inadequate effect. The mechanisms responsible for the variations are now understood, at least in part, and are related to the absorption, distribution, excretion, metabolism, and interactions of the drug.

An excellent correlation between plasma level and pharmacological effect of some drugs has been observed in human studies.1 However, individual differences in the rates of metabolism may account for a thirtyfold variation in