The genetic polymorphism of debrisoquine/sparteine metabolism--clinical aspects

It has been established that the metabolism of more than twenty drugs, including antiarrhythmics, beta-adrenoceptor antagonists, antidepressants, opiates and neuroleptics is catalyzed by cytochrome P-450dbl. The activity of this P-450 isozyme is under genetic rather than environmental control. This article discusses the therapeutic implications for each of the classes of drugs affected by this genetic polymorphism in drug metabolism. Not only are the problems associated with poor metabolizers who are unable to metabolize the compounds discussed, but it is also emphasized that it is difficult to attain therapeutic plasma concentrations for some drugs in high activity extensive metabolizers.