Title:Drug Interactions with Angiotensin Receptor Blockers: Role of Human Cytochromes P450
VOLUME: 17 ISSUE: 7
Author(s):Ruirui Yang, Zhiqiang Luo, Yang Liu, Mohan Sun, Ling Zheng, Yingying Chen, Yanping Li, Hao Wang, Lingzhu Chen, Ming Wu and Huihui Zhao
Affiliation: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.
Keywords:Angiotensin receptor blockers (ARBs), clinical relevance, CYP450 enzymes, hypertension, mechanisms, pharmacokinetic interactions.
Abstract:Background: 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.
Methods: 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’.
Results: 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.
Conclusion: 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.
