Department of Pharmacy Practice, College of Pharmacy, Purdue University, 1001 West 10th St., Indianapolis, IN 46202, USA.
Am J Manag Care. 2011 Sep;17 Suppl 11:S276-87.
Pharmacokinetic drug-drug interactions (DDIs) involving opioid analgesics can be problematic. Opioids are widely used, have a narrow therapeutic index, and can be associated with severe toxicity. The purpose of this review is to describe pharmacokinetic DDIs associated with opioids frequently encountered in managed care settings (morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, tramadol, and methadone). An introduction to the pharmacokinetic basis of DDIs is provided, and potential DDIs associated with opioids are reviewed. Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects. Conversely, opioids that are not metabolized by that system (morphine, oxymorphone, and hydromorphone) tend to be involved in fewer CYP450-associated pharmacokinetic DDIs.
涉及阿片类镇痛药的药物代谢动力学药物相互作用（DDI）可能会引发问题。阿片类药物广泛使用，治疗指数狭窄，可能会引起严重毒性。本综述的目的是描述在管理式医疗环境中经常遇到的与阿片类药物相关的药物代谢动力学 DDI（吗啡、可待因、羟考酮、羟吗啡酮、氢可酮、氢吗啡酮、芬太尼、曲马多和美沙酮）。本文提供了 DDI 的药物代谢动力学基础介绍，并对与阿片类药物相关的潜在 DDI 进行了回顾。经细胞色素 P450（CYP450）系统代谢的阿片类药物（可待因、羟考酮、氢可酮、芬太尼、曲马多和美沙酮）与许多 DDI 相关，这些 DDI 可导致阿片类药物作用降低或阿片类药物作用过度。相反，不通过该系统代谢的阿片类药物（吗啡、羟吗啡酮和氢吗啡酮）则往往较少涉及 CYP450 相关的药物代谢动力学 DDI。
