Gelissen Ingrid C, McLachlan Andrew J
Faculty of Pharmacy, University of Sydney, NSW, Australia.
Faculty of Pharmacy, University of Sydney, NSW, Australia; Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia.
Pharmacol Res. 2014 Oct;88:99-106. doi: 10.1016/j.phrs.2013.12.002. Epub 2013 Dec 21.
The statin class of cholesterol-lowering drugs have been used for decades to successfully lower plasma cholesterol concentrations and cardiovascular risk. Adverse effects of statins are generally considered mild, but increase with age of patients and polypharmacy. One aspect of statin therapy that is still difficult for prescribers to predict is the individual's response to statin therapy. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect statin efficacy and safety. In this review, a number of candidates that affect statin pharmacokinetics and pharmacodynamics are discussed. Some of these candidates, in particular those involved in import and efflux of statins, have now been linked to increased risk of side effects. Furthermore, pharmacogenomic studies continue to reveal new players that are involved in the fine-tuning of the complex regulation of cholesterol homeostasis and response to statins.
他汀类降胆固醇药物已使用数十年,成功降低了血浆胆固醇浓度并降低了心血管疾病风险。他汀类药物的不良反应通常被认为较为轻微,但会随着患者年龄增长和联合用药而增加。他汀类药物治疗中,医生仍难以预测的一个方面是个体对他汀类药物治疗的反应。药物基因组学领域的最新进展表明,候选基因的变异会影响他汀类药物的疗效和安全性。在本综述中,将讨论一些影响他汀类药物药代动力学和药效学的候选基因。其中一些候选基因,特别是那些参与他汀类药物摄取和外排的基因,现已被证实与副作用风险增加有关。此外,药物基因组学研究不断揭示参与精细调节胆固醇稳态和对他汀类药物反应的新因素。