文献_Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions.pdf

American Journal of Therapeutics 16, 155–163 (2009) Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions Judy W. M. Cheng, PharmD, MPH, FCCP, BCPS,1 William H. Frishman, MD,2 2 and Wilbert S. Aronow, MD * Cytochrome P (CYP) 450 is a superfamily of hemoproteins that play an important role in the metabolism of steroid hormones, fatty acids, and many medications. Many agents used for management of cardiovascular diseases are substrates, inhibitors, or inducers of CYP450 enzymes. When two agents that are substrates, inhibitors, or inducers of CYP450 are administered together, drug interactions with significant clinical consequences may occur. This review discusses CYP450- mediated cardiovascular drug interactions as well as noncardiovascular drug interactions that produced significant cardiovascular side effects. The principles in predicting drug interactions are also discussed. Keywords: Cytochrome P 450, drug interactions, cardiovascular drugs INTRODUCTION the enzyme (eg, CYP3A4). CYP1, CYP2, and CYP3 are the three families responsible for most drug and Cytochrome P (CYP) 450 is a superfamily of hemo- carcinogen metabolism.1 The CYP1 family may also proteins found in human liver and other tissues such as play a role in carcinogenic activation,1 whereas CYP2 the gastrointestinal tract that play an important role in and CYP3 are characterized by th