Genetic Polymorphism of Sparteine/Debrisoquine Oxidation: A Reappraisal

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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.