Pharmacogenetics of drug metabolising enzymes: importance for personalised medicine.

Abstract

The number of polymorphisms identified in genes encoding drug metabolising enzymes, drug transporters, and receptors is rapidly increasing. In many cases, these genetic factors have a major impact on the pharmacokinetics and pharmacodynamics of a particular drug and thereby influence the sensitivity to such drug in an individual patient with a certain genotype. The highest impact is seen for drugs with a narrow therapeutic index, with important examples emerging from treatment with antidepressants, oral anticoagulants, and cytostatics, which are metabolised by the polymorphic enzymes cytochrome P450 2D6 (CYP2D6), cytochrome P450 2C9 (CYP2C9), and thiopurine-S-methyltransferase (TPMT), respectively. In order to apply the increasing amount of pharmacogenetic knowledge to clinical practise, specific dosage recommendations based on genotypes will have to be developed to guide the clinician, and these recommendations will have to be evaluated in prospective clinical studies. Such development will lead to a patient-tailored drug therapy which hopefully would be more efficient and will result in fewer adverse drug reactions.