Hallinan Richard, Crettol Séverine, Agho Kingsley, Attia John, Besson Jacques, Croquette-Krokar Marina, Hämmig Robert, Déglon Jean-Jacques, Byrne Andrew, Ray John, Somogyi Andrew A, Eap Chin B
The Byrne Surgery, Redfern, NSW, Australia.
Eur J Clin Pharmacol. 2009 Nov;65(11):1113-20. doi: 10.1007/s00228-009-0706-8. Epub 2009 Jul 29.
To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics.
Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose.
Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4.
Cannabis use and higher methadone doses in MMT could in part be a response to-or a cause of-more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.
评估美沙酮维持治疗（MMT）中烟草、酒精、大麻和苯二氮䓬类药物的使用情况，将其作为美沙酮药代动力学变异性的潜在来源。
对77名澳大利亚和74名瑞士MMT患者的血浆谷浓度（R）-和（S）-美沙酮进行测量，这些患者除苯二氮䓬类药物外未使用其他药物。对主要指标血浆美沙酮浓度/剂量进行简单和多元回归分析。
大麻和美沙酮剂量与较低的24小时血浆（R）-和（S）-美沙酮浓度/剂量显著相关。包含这些变量的模型分别解释了（R）-和（S）-美沙酮浓度/剂量变化的14%-16%和17%-25%。对仅使用CYP3A4代谢的苯二氮䓬类药物的61名患者进行分析，结果显示此类药物与较高的（R）-浓度/剂量相关，这与CYP3A4的潜在竞争性抑制作用一致。
MMT中使用大麻和较高的美沙酮剂量可能部分是对美沙酮清除更快的一种反应或原因。在未来关于MMT中美沙酮药代动力学的研究中，应控制大麻和苯二氮䓬类药物的影响。
