Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
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Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz · Oct 2006
Review Comparative Study[State of the art of pharmacogenetic diagnostics in drug therapy].
Individual differences in the effect and side effect of drugs are partly due to genetic factors (genetic polymorphisms). The responsible polymorphisms lie in genes encoding for drug metabolism and transport but also in direct and indirect drug targets. While genetic variants in pharmacokinetic structures exert effects on drug efficacy via the differences in drug exposure, polymorphisms in drug targets can directly affect clinical efficacy and may lead to a broad variation spectrum between inefficacy and severe side effects. ⋯ The most important reason, however, may be that most results of pharmacogenetic research are so far not translated into therapeutically usable conclusions and therapy recommendations. Thus, testing for a genotype without concrete consequences for the drug therapy of an individual patient does not make sense. Pharmacogenetic research, thereby, stands in many cases at the threshold to clinical applicability and in many cases, for instance for the genotyping for thiopurine methyltransferase polymorphisms prior to azathioprine therapy or of dihydropyrimidine dehydrogenase polymorphisms prior to treatment with 5-fluorouracil, as well as for diagnostics of CYP2D6 before therapy with certain tricyclic antidepressants and neuroleptics, one would ask already today whether a such drug therapy is still responsible without pharmacogenetic diagnostics.