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[Individualized pharmacotherapy based on cytochrome P-450 (CYP) genotyping]
Per Wiik Johansen1, Stein Bergan, Helge Rootwelt
1Avdeling for klinisk farmakologi, Rikshospitalet 0027 Oslo. per.w.johansen@rikshospitalet.no
Background:
Genetic polymorphisms of the drug-metabolising cytochrome P-450 (CYP) enzymes CYP2C9, CYP2C19 and CYP2D6 have been characterized, and several of these variants lead to reduced or absent activity. This is of clinical importance mainly in patients having two non-functional alleles, phenotypically characterised as "poor metabolisers" (1-10% of Caucasians). Since most drugs are transformed into inactive or less active metabolites, "poor metabolisers" are at increased risk of developing drug induced adverse reactions.
Material And Methods:
Studies of relevant literature (MedLine search) in addition to our own experiences, show that CYP genotyping can predict the phenotype and thereby explain some abnormal drug responses and may be used to individualize pharmacotherapy.
Results:
At present, CYP genotyping (CYP2C9/2C19/2D6) is most frequently requested in psychiatry and anticoagulant therapy, but the field is expanding. Important factors for implementation of pharmacogenetic methods are accuracy of diagnosis, quality of reports, response time, and cost.
Interpretation:
Pharmacogenetic analyses will significantly contribute to reducing treatment costs for drug-induced adverse reactions and costs of sick leave, by predicting the best drug and the most effective and safest dosage. The expenses of full genotyping (CYP2C9/2C19/2D6) are equivalent to one day of sick leave. One might ask: Are pharmacogenetic analyses coming to the point where they drive down costs incurred by illness?