Department of Pharmacy Practice, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Ann Pharmacother. 2011 Jun;45(6):e34. doi: 10.1345/aph.1P759. Epub 2011 Jun 10.
To report the potential clinically significant pharmacokinetic interaction that may result from smoking cessation in patients on methadone maintenance therapy.
A 46-year-old white man was admitted to the step-down intensive care unit with decreased respirations and altered mental status related to methadone toxicity. The patient had been on a stable dose of methadone for chronic back pain, and he reported a 1 pack per day, 33-year history of cigarette smoking. After methadone was held for 3 days, his mental status improved. It was later revealed that he had initiated smoking cessation. He was discharged home on a reduced dose of methadone with no further complications.
While the potential for toxicity exists for patients who are maintained on methadone and decrease the number of cigarettes they smoke, to our knowledge, there is no recent peer-reviewed literature on this interaction. Methadone is a synthetic opioid primarily metabolized by CYP3A4 and, to a lesser degree, by other isoenzymes, including CYP1A2. Polycyclic aromatic hydrocarbons found in tobacco smoke are known CYP1A2 inducers. Decreased intake of cigarette smoke can lead to a reduction in methadone metabolism, resulting in higher serum concentrations. Our case is an example of methadone toxicity secondary to smoking cessation in a patient on methadone maintenance therapy. An objective causality assessment based on the Horn Drug Interaction Probability Scale revealed the interaction to be probable.
Patients on methadone should be monitored for signs of methadone toxicity upon the start of smoking cessation, and the dose of methadone should be adjusted accordingly. Additional information and reports cautioning clinicians and patients about this potential interaction would be beneficial.
报告可能由于美沙酮维持治疗患者戒烟而导致的具有临床意义的潜在药物动力学相互作用。
一名 46 岁白人男性因美沙酮中毒导致呼吸减少和精神状态改变而被收入重症监护病房。该患者因慢性背痛而接受稳定剂量的美沙酮治疗，且他有每日 1 包、33 年吸烟史。美沙酮停用 3 天后，其精神状态改善。后来发现他已经开始戒烟。他出院时美沙酮剂量减少，没有出现进一步并发症。
虽然对于减少吸烟量的美沙酮维持治疗患者存在毒性的潜在风险，但据我们所知，最近没有关于这种相互作用的同行评议文献。美沙酮是一种主要通过 CYP3A4 代谢的合成阿片类药物，在较小程度上通过其他同工酶代谢，包括 CYP1A2。烟草烟雾中发现的多环芳烃是已知的 CYP1A2 诱导剂。减少吸烟量可导致美沙酮代谢减少，从而导致血清浓度升高。我们的病例是美沙酮维持治疗患者戒烟后出现美沙酮中毒的一个例子。根据 Horn 药物相互作用概率量表进行的客观因果关系评估显示，该相互作用是可能的。
开始戒烟时，应监测美沙酮维持治疗患者是否有美沙酮中毒迹象，并相应调整美沙酮剂量。提供更多关于这种潜在相互作用的信息和报告，提醒临床医生和患者注意，将是有益的。
