Schlatter J, Madras J L, Saulnier J L, Poujade F
Service Pharmacie, Centre Hospitalier de Gonesse.
Presse Med. 1999 Sep 4;28(25):1381-4.
Methadone is metabolized by cytochrome P450 enzymes in the liver microsomes and binds selectively to mu opiate receptors. Drugs metabolized by these enzymes or mu receptor competitors can modify the action of methadone. Genetic polymorphism influences plasma concentrations of the active levo enantiomer and thus clinical efficacy. ANTITUBERCULOSIS DRUGS: Rifampicin lowers methadome plasma levels so dose must be adapted. Rifabutin does not affect methadone kinetics. ANTI-EPILEPSY DRUGS: Phenytoin lowers blood levels of methadone by about 50% in 3 to 4 days. Other anti-epilepsy enzyme inducers (phenobarbital, carbamazepine) increase methadone metabolism. ANTI-VIRAL DRUGS: The area under the curve of plasma concentrations of zidovudine in presence of methadone increase by 43%, increasing the risk of undesirable effects. PSYCHOTROPES: Plasma levels of methadone increase by 20 to 100% in the presence of fluvoxamine. The benzodiazepine-methadone combination can be fatal due to respiratory depression. OTHER DRUGS: Brupenophine is a methadone agonist at the dose of 1 and 2 mg. Chronic alcoholism reduces the area under the curve while acute alcoholism increases it. Pure morphine agonists raise a major risk of respiratory depression while partial agonists favor the development of withdrawal symptoms.
美沙酮在肝脏微粒体中通过细胞色素P450酶代谢，并选择性地与μ阿片受体结合。由这些酶代谢的药物或μ受体拮抗剂可改变美沙酮的作用。基因多态性影响活性左旋对映体的血浆浓度，进而影响临床疗效。
利福平会降低美沙酮的血浆水平，因此必须调整剂量。利福布汀不影响美沙酮的药代动力学。
苯妥英在3至4天内可使美沙酮的血药水平降低约50%。其他抗癫痫酶诱导剂（苯巴比妥、卡马西平）会增加美沙酮的代谢。
在美沙酮存在的情况下，齐多夫定血浆浓度曲线下面积增加43%，增加了不良反应的风险。
在氟伏沙明存在的情况下，美沙酮的血浆水平会升高20%至100%。苯二氮䓬类药物与美沙酮合用可能因呼吸抑制而致命。
布普诺啡在1毫克和2毫克剂量时是美沙酮激动剂。慢性酒精中毒会降低曲线下面积，而急性酒精中毒则会增加该面积。纯吗啡激动剂会增加呼吸抑制的主要风险，而部分激动剂则会促使戒断症状的出现。
