engleski

Pharmacogenetics: role of clinical laboratory in therapy optimatisation

Adverse drug reactions have recently been reported to occur as the fourth to sixth cause of death in hospital patients, accounting for one of 15 (6.7%) hospital admissions, whereby one of 300 (0.3%) such reactions has a fatal outcome. Adverse drug reaction can be induced by some transient causes such as drug metabolizing enzyme inhibition or induction, or by some permanent cause such as genetic mutation or gene deletion-polymorphism. Genetic polymorphism of drug metabolizing enzymes, drug transporters or drug receptors can be studied by pharmacogenetics, a novel field of pharmacologic sciences investigating the linkage between an individual’s genome and the individual’s ability to metabolize a drug. Genetic polymorphism has been related to three classes of phenotypes according to the ability to metabolize a drug. The phenotype of extensive metabolism (EM) of drug is characteristic of the normal population. The phenotype of poor metabolism (PM) is associated with accumulation of specific drug substrates and is a typical autosomal recessive trait generated by mutation and/or deletion of both alleles responsible for phenotypic expression. The phenotype of ultra-extensive metabolism (UEM) manifests as increased drug metabolism and is an autosomal dominant trait resulting from gene amplification. Recently, genetic polymorphism of the alleles coding for drug metabolizing enzymes, drug transporters and receptors can be determined by the methods of molecular biology in clinical laboratories. Pretreatment genotyping allows identifying the subjects prone to adverse drug reactions, to choose an individual’s optimal drug dose, and to prevent undesired drug reactions. Clinical application of the information obtained by genotyping and phenotyping in the relation between clinical laboratory and clinical practitioners should answer the following questions: • When genotyping is clinically indicated? • What advantages are expected from their introduction in the therapy process? • Do these strategies provide cost-effective health care paradigms?

pharmacogenetics; therapy optimisation; clinical laboratory

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