A genetically determined impairment in the ability to oxidise sparteine and debriso-quine also affects the oxidation of several other drugs. This impairment in oxidation may result in accumulation of the associated drugs and in an increased susceptibility to adverse reactions from these drugs.
Dunedin houses the New Zealand national centre for the collation and study of adverse drug reactions. Included among the reporting schemes is an intensified monitoring system for newly released drugs, in which physicians report all clinical events occurring during treatment with the drugs under surveillance. The centre thus has available extensive records of names and addresses of prescribes and patients who have been reported as experiencing an adverse event while receiving drug therapy.
We investigated the association between genetically poor oxidation of sparteine and adverse reactions to drugs selected as possibly sharing the sparteine/debrisoquine oxidation pathway; these included perhexiline, metoprolol, debrisoquine, piroxicam, mianserin and nifedipine. A kit containing instructions, a sparteine capsule and a container for urine collection was sent to physicians who reported adverse reactions or events to one of the above drugs for forwarding to the patient.
It appeared possible, after assays of returned urine for sparteine and its metabolites, that adverse reactions to nifedipine were associated with genetically poor oxidation. However, a retrospective study in which sparteine metabolic ratios of 11 patients who had been withdrawn from nifedipine because of adverse reactions were compared with those of 37 patients who had continued on nifedipine without adverse effects did not confirm that adverse reactions to nifedipine were more common among genetically poor oxidisers of sparteine.
Further prospective investigations involving the selected drugs are required to determine whether phenotyping for sparteine oxidation status will assist clinicians in predicting susceptibility to adverse reactions. The study demonstrated that pharmacogenetic, or other, investigations of factors associated with adverse drug reactions can be readily carried out in the general population.
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