Yang Ruirui, Luo Zhiqiang, Liu Yang, Sun Mohan, Zheng Ling, Chen Yingying, Li Yanping, Wang Hao, Chen Lingzhu, Wu Ming, Zhao Huihui
School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6, Zhonghuan South Road, Wangjing, Chaoyang District, Beijing 100102, P.R. China.
Science and Technology Department, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, P.R. China.
Curr Drug Metab. 2016;17(7):681-91. doi: 10.2174/1389200217666160524143843.
Angiotensin receptor blockers (ARBs) are the most recent class of agents for the treatment of hypertension. However, ARBs may cause a low incidence of headache, upper respiratory infection, back pain, muscle cramps, fatigue, dizziness, and many other side effects. In some cases, such toxicity is associated with pharmacokinetic alterations.
The cytochrome P450 (CYP) enzyme system plays an important role in a lot of clinically important pharmacokinetic drug interactions. To identify relevant studies on drug-drug and food-drug pharmacokinetic interactions with the ARBs, a literature search of Google Scholar was performed from January 1994 to June 2015, with the following keywords: 'losartan', 'valsartan,' 'candesartan,' 'irbesartan,' 'telmisartan,' 'eprosartan,' 'olmesartan,' and 'azilsartan', combined with the keyword 'pharmacokinetic interactions' and 'CYP'.
Based on the literatures published, it has been demonstrated that pharmacokinetic interactions of losartan with other agents are mainly via CYP2C9- and CYP3A4-mediated, the role played by CYP enzyme system in the metabolism of valsartan, candesartan, irbesartan, and azilsartan appears modest, and cytochrome P450 system has no influence on the metabolism of telmisartan, eprosartan, olmesartan. Therefore, according to these pharmacokinetic findings, no dosage adjustment is recommended when eprosartan, telmisartan and olmesartan are combined with other pharmacological agents in patients with hypertension.
This review summarize the available data on cytochrome P450 - related drug-drug interactions reported in the literature for the eight ARBs. Knowledge of the pharmacokinetic properties of the ARBs should allow the avoidance of the majority of drug interactions without compromising therapeutic benefits.
血管紧张素受体阻滞剂（ARBs）是治疗高血压的最新一类药物。然而，ARBs可能会引起低发生率的头痛、上呼吸道感染、背痛、肌肉痉挛、疲劳、头晕以及许多其他副作用。在某些情况下，这种毒性与药代动力学改变有关。
细胞色素P450（CYP）酶系统在许多具有临床重要性的药物药代动力学相互作用中起重要作用。为了确定与ARBs相关的药物-药物和食物-药物药代动力学相互作用的相关研究，于1994年1月至2015年6月在谷歌学术上进行了文献检索，使用了以下关键词：“氯沙坦”、“缬沙坦”、“坎地沙坦”、“厄贝沙坦”、“替米沙坦”、“依普罗沙坦”、“奥美沙坦”和“阿齐沙坦”，并与关键词“药代动力学相互作用”和“CYP”相结合。
根据已发表的文献，已证明氯沙坦与其他药物的药代动力学相互作用主要通过CYP2C9和CYP3A4介导，CYP酶系统在缬沙坦、坎地沙坦、厄贝沙坦和阿齐沙坦代谢中所起的作用似乎不大，并且细胞色素P450系统对替米沙坦、依普罗沙坦、奥美沙坦的代谢没有影响。因此，根据这些药代动力学研究结果，高血压患者将依普罗沙坦、替米沙坦和奥美沙坦与其他药物联合使用时，不建议调整剂量。
本综述总结了文献中报道的关于这八种ARBs与细胞色素P450相关的药物-药物相互作用的现有数据。了解ARBs的药代动力学特性应有助于避免大多数药物相互作用，同时不影响治疗效果。
