Kirchheiner J, Sasse J, Roots I, Brockmöller J, Bauer M
Institut für Klinische Pharmakologie, Universitätsmedizin Berlin.
Nervenarzt. 2005 Nov;76(11):1340-54. doi: 10.1007/s00115-005-1915-8.
The pharmacokinetics and effect of antidepressants are influenced by genetic factors. Modern methods of genotyping allow fast and inexpensive identification of genetic variants and thus can be used in clinical diagnostics to improve the tolerance to drug therapy. Numerous studies have investigated the significance of genetic variants in drug-metabolizing enzymes, drug and natural substrate transporters, neurotransmitter receptors, and molecules involved in signal transduction. While the interindividual differences in oral clearance, half-life, and bioavailability caused by genetic variants in the cytochrome P450 liver enzymes can be overcome by individual adjustment of dosage according to certain genotypes, the effects of genetic variants in antidepressive target structures are more difficult to translate into clinical recommendations. This article gives an overview of the currently available literature and points to situations in which the determination of pharmacogenetic variants might change drug therapy or therapeutic strategies for the individual patient. Dose adjustments for common antidepressant drugs based upon differences in pharmacokinetic parameters caused by genetic variability will be given.
抗抑郁药的药代动力学和疗效受遗传因素影响。现代基因分型方法能够快速且低成本地鉴定基因变异,因此可用于临床诊断,以提高对药物治疗的耐受性。众多研究探讨了基因变异在药物代谢酶、药物及天然底物转运体、神经递质受体以及信号转导相关分子中的意义。虽然细胞色素P450肝酶基因变异导致的口服清除率、半衰期和生物利用度的个体差异可通过根据特定基因型进行个体剂量调整来克服,但抗抑郁靶点结构中基因变异的影响更难转化为临床建议。本文概述了当前可得的文献,并指出药物遗传学变异的测定可能改变个体患者药物治疗或治疗策略的情况。还将给出基于遗传变异性导致的药代动力学参数差异对常见抗抑郁药进行剂量调整的方法。