The Polymorphic Metabolism of Dextromethorphan

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Abstract
The ability of healthy male volunteers to metabolize a 30-mg oral dose of dextromethorphan (DM) was studied in 252 Americans. Two blood samples were collected at four and 24 hours after administration of the dose. The resulting plasma was analyzed for unchanged DM. The volunteers were classified as slow, intermediate, or fast metabolizers on the basis of plasma concentrations of DM. Further differentiation of slow and intermediate metabolizers was achieved by comparing the two-point estimates of elimination-rate constants. In the population studied, 84.3% were fast DM metabolizers, 6.8% were intermediate metabolizers, and 8.8% were slow metabolizers. Previous reports have related the slow DM metabolizers to slow debrisoquin metabolizers, but no such correlations have been achieved with intermediate DM metabolizers. These intermediate DM metabolizers may suggest a new polymorphism not related to debrisoquin or may suggest that “debrisoquin gene” regulation is more complex than originally suggested.