Genetic polymorphism of sparteine/debrisoquine oxidation: a reappraisal

Abstract

Polymorphic oxidation of the sparteine/debrisoquine-type has been shown to account for much of the interindividual variation in the metabolism, pharmacokinetics and pharmacodynamics of an increasing number of drugs, including some antiarrhythmic, antidepressant and beta-adrenoceptor antagonist agents. Impaired hydroxylation of these drugs results from the absence of the enzyme cytochrome P450IID6 in the livers of poor metabolisers, who constitute 6% to 10% of Caucasian populations. The clinical importance of the phenomenon has to be explored further and for most sparteine/debrisoquine-related substrates there is a need for controlled prospective studies to define the consequences to the patient of impaired or enhanced drug oxidation.