Kirchheiner Julia, Rodriguez-Antona Cristina
Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany.
CNS Drugs. 2009;23(3):181-91. doi: 10.2165/00023210-200923030-00001.
The specific reaction toward a given drug varies a lot between individuals and, for many drugs, pharmacogenetic polymorphisms are known to affect biotransformation and clinical outcome. Estimation of the individual's drug-metabolizing capacity can be undertaken by genotyping drug-metabolizing enzymes involved in the respective drug metabolism. Consequences that arise from genotyping may be the adjustment of dose according to genotype, choice of therapeutic strategy, or even choice of drug. One of the first fields where the clinical application of pharmacogenetics may be used is in that of antipsychotic and antidepressant drug treatment because there is a special need for individualized therapy in psychiatry. The pharmacokinetics of many TCAs, some SSRIs and other antidepressant drugs is significantly altered by polymorphisms; however, some controversy still exists as to whether therapeutic efficacy may be improved and/or adverse events can be prevented by genetically driven adjustment of drug dosage. Pharmacogenetic diagnostics may be an important factor in individualizing drug treatment according to the genetic make-up of the patients. However, routine application of pharmacogenetic dose adjustment in clinical practice requires prospective validation.
个体对特定药物的反应差异很大,而且对于许多药物来说,已知药物遗传多态性会影响生物转化和临床结果。通过对参与相应药物代谢的药物代谢酶进行基因分型,可以评估个体的药物代谢能力。基因分型的结果可能是根据基因型调整剂量、选择治疗策略,甚至选择药物。药物遗传学临床应用的首批领域之一可能是抗精神病药物和抗抑郁药物治疗,因为精神病学特别需要个体化治疗。许多三环类抗抑郁药、一些选择性5-羟色胺再摄取抑制剂和其他抗抑郁药物的药代动力学因多态性而显著改变;然而,对于通过基因驱动调整药物剂量是否可以提高治疗效果和/或预防不良事件,仍存在一些争议。药物遗传学诊断可能是根据患者的基因构成实现个体化药物治疗的一个重要因素。然而,在临床实践中常规应用药物遗传学剂量调整需要前瞻性验证。