Herman R J
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon.
CMAJ. 1999 Nov 16;161(10):1281-6.
Drug interactions commonly occur in patients receiving treatment with multiple medications. Most interactions remain unrecognized because drugs, in general, have a wide margin of safety or because the extent of change in drug levels is small when compared with the variation normally seen in clinical therapy. All drug interactions have a pharmacokinetic or pharmacodynamic basis and are predictable given an understanding of the pharmacology of the drugs involved. Drugs most liable to pose problems are those having concentration-dependent toxicity within, or close to, the therapeutic range; those with steep dose-response curves; those having high first-pass metabolism or those with a single, inhibitable route of elimination. Knowing which drugs possess these intrinsic characteristics, together with a knowledge of hepatic P-450 metabolism and common enzyme-inducing and enzyme-inhibiting drugs, can greatly assist physicians in predicting interactions that may be clinically relevant. This article reviews the pharmacology of drug interactions that can occur with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) to illustrate the scope of the problem and the ways in which physicians may manage this important therapeutic class of drugs.
药物相互作用常见于接受多种药物治疗的患者中。大多数相互作用未被识别，这是因为一般来说药物有较宽的安全范围，或者与临床治疗中通常所见的变化相比，药物水平的变化程度较小。所有药物相互作用都有药代动力学或药效学基础，并且在了解所涉及药物的药理学知识后是可预测的。最容易引发问题的药物是那些在治疗范围内或接近治疗范围时具有浓度依赖性毒性的药物；那些具有陡峭剂量反应曲线的药物；那些具有高首过代谢的药物或那些具有单一、可抑制消除途径的药物。了解哪些药物具有这些内在特性，再结合对肝P - 450代谢以及常见酶诱导和酶抑制药物的了解，能够极大地帮助医生预测可能具有临床相关性的相互作用。本文回顾了与羟甲基戊二酰辅酶A（HMG - CoA）还原酶抑制剂（他汀类药物）可能发生的药物相互作用的药理学，以说明问题的范围以及医生管理这类重要治疗药物的方法。
