Adverse drug reaction reporting and retrospective phenotyping for oxidation polymorphism.
A genetically determined impairment in the ability to oxidase sparteine and debrisoquine 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 prescribers 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Clark
D W
DW
Department of Pharmacology, University of Otago Medical School, Dunedine.
Edwards
I R
IR
D003647:Debrisoquin / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008790:Metoprolol / Q000009:adverse effects / Q000378:metabolism; D009543:Nifedipine / Q000009:adverse effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010641:Phenotype; D010894:Piroxicam / Q000009:adverse effects / Q000378:metabolism; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013034:Sparteine / Q000009:adverse effects / Q000378:metabolism*
D007546:Isoquinolines; D010894:Piroxicam; D013034:Sparteine; D008790:Metoprolol; D009543:Nifedipine; D003647:Debrisoquin