Metabolism and Disposition of Prescription Opioids: A Review.
Metabolism and Disposition of Prescription Opioids: A Review.
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发表时间：
2015-07
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通讯作者：
Anne Depriest;Brandi L. Puet;A. Holt;A. Roberts;E. Cone
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作者：
Anne Depriest;Brandi L. Puet;A. Holt;A. Roberts;E. Cone
阿片类镇痛药通常用于急性和慢性疼痛，但容易被滥用。因此，毒理学测试程序经常用于法医和临床应用。了解阿片类药物的代谢和处置对于评估毒性风险至关重要，在某些情况下，还可以提供有关治疗失败风险的额外信息。由细胞色素p450 （CYP450）酶系统代谢的阿片类药物可能与药物相互作用有关，包括可待因、氢可酮、羟考酮、芬太尼、哌替啶、美沙酮、丁丙诺啡和曲马多。CYP2D6代谢具有多态性，可待因、曲马多、羟考酮和氢可酮的药理学检测已被研究。美沙酮CYP2B6药理学检测可降低与s -对映体相关的心脏毒性风险。主要由尿苷5′-二磷酸葡萄糖醛基转移酶（UGT）代谢的阿片类药物包括吗啡、氢吗啡酮、二氢可待因、氧吗啡酮、左旋orphanol和tapentadol。母体和代谢物的处置描述为血液，口服液和尿液。母体药物最常在血液和口服液中检测到，而代谢物通常在尿液中占主导地位。大多数阿片类药物的口服液/血比超过1，使其成为测试这类药物的极好替代基质。可待因、氢可酮和羟考酮的代谢物可在市场上买到，对代谢的了解是正确解释的必要条件。
Opioid analgesics are commonly prescribed for acute and chronic pain, but are subject to abuse. Consequently, toxicology testing programs are frequently implemented for both forensic and clinical applications. Understanding opioid metabolism and disposition is essential for assessing risk of toxicity and, in some cases, providing additional information regarding risk of therapeutic failure. Opioids significantly metabolized by the cytochromeP450 (CYP450) enzyme system maybe subjectto drug-drug interactions, including codeine, hydrocodone, oxycodone, fentanyl, meperidine, methadone, buprenorphine, and tramadol. CYP2D6 metabolism is polymorphic, and pharmacogenetic testing has been investigated for codeine, tramadol, oxycodone, and hydrocodone. CYP2B6 pharmacogenetic testing of methadone may reduce the risk of cardiac toxicity associated with the S-enantiomer. Opioids metabolized primarily by uridine 5'-diphospho-glucuronsyltransferase (UGT) enzymes include morphine, hydromorphone, dihydrocodeine, oxymorphone, levorphanol, and tapentadol. Parent and metabolite disposition is described for blood, oral fluid, and urine. Parent drug is most commonly detected in blood and oral fluid, whereas metabolites typically predominate in urine. Oral fluid/blood ratios exceed 1 for most opioids, making this an excellent alternative matrix for testing of this drug class. Metabolites of codeine, hydrocodone, and oxycodone are commercially available, and knowledge of metabolism is necessary for correct interpretation.