Cohen L J, De Vane C L
University of Oklahoma Colleges of Pharmacy and Medicine, University of Oklahoma Health Sciences center, Oklahoma City 73117, USA.
Ann Pharmacother. 1996 Dec;30(12):1471-80. doi: 10.1177/106002809603001216.
To review available data on pharmacokinetic and pharmacogenetic influences on the response to antidepressant therapy, analyze the mechanisms for and clinical significance of pharmacokinetic and pharmacogenetic differences, and explain the implications of pharmacokinetics and pharmacogenetics for patient care.
A MEDLINE search of English-language clinical studies, abstracts, and review articles on antidepressant pharmacokinetics, pharmacogenetics, and drug interactions was used to identify pertinent literature.
The pharmacokinetic profiles of selected antidepressants are reviewed and the impact of hepatic microsomal enzymes on antidepressant metabolism is considered. How phenotypic differences influence the metabolism of antidepressant drug therapy is addressed. To evaluate the clinical implications of these pharmacokinetic and pharmacogenetic considerations, the findings of studies designed to elucidate drug interactions involving antidepressant agents are discussed.
Differences in antidepressant plasma concentrations, and possibly safety, are caused by polymorphism in the genes that encode some of the cytochrome P450 isoenzymes that metabolize antidepressants. The isoenzymes 1A2, 2C9/19, 2D6, and 3A4 are the major enzymes that catalyze antidepressant metabolic reactions. Antidepressants can be either substrates or inhibitors of these enzymes, which also metabolize many other pharmacologic agents. Although the cytochrome enzymes that metabolize antidepressants have not been fully characterized, interaction profiles of the newer antidepressants are becoming more clearly defined. Determining patient phenotypes is not practical in the clinical setting, but an awareness of the possibility of genetic polymorphism in antidepressant metabolism may help explain therapeutic failure or toxicity, help predict the likelihood of drug interactions, and help clinicians better manage antidepressant drug therapy.
回顾有关药代动力学和药物遗传学对抗抑郁治疗反应影响的现有数据，分析药代动力学和药物遗传学差异的机制及临床意义，并解释药代动力学和药物遗传学对患者护理的影响。
通过对MEDLINE数据库进行检索，查找关于抗抑郁药药代动力学、药物遗传学及药物相互作用的英文临床研究、摘要和综述文章，以确定相关文献。
回顾了所选抗抑郁药的药代动力学特征，并考虑了肝微粒体酶对抗抑郁药代谢的影响。探讨了表型差异如何影响抗抑郁药物治疗的代谢。为评估这些药代动力学和药物遗传学因素的临床意义，讨论了旨在阐明涉及抗抑郁药的药物相互作用的研究结果。
编码某些参与抗抑郁药代谢的细胞色素P450同工酶的基因多态性导致了抗抑郁药血浆浓度的差异，可能还影响安全性。同工酶1A2、2C9/19、2D6和3A4是催化抗抑郁药代谢反应的主要酶。抗抑郁药可以是这些酶的底物或抑制剂，而这些酶也参与许多其他药物的代谢。尽管参与抗抑郁药代谢的细胞色素酶尚未完全明确，但新型抗抑郁药的相互作用特征正变得更加清晰。在临床环境中确定患者表型并不实际，但了解抗抑郁药代谢中基因多态性的可能性可能有助于解释治疗失败或毒性，有助于预测药物相互作用的可能性，并有助于临床医生更好地管理抗抑郁药物治疗。
