Brown L S, Sawyer R C, Li R, Cobb M N, Colborn D C, Narang P K
Addiction Research and Treatment Corporation, Brooklyn, NY 11201, USA.
Drug Alcohol Depend. 1996 Dec 2;43(1-2):71-7. doi: 10.1016/s0376-8716(97)84352-9.
Rifampin, an agent known to decrease the half-life of methadone, and rifabutin are two rifamycins that are structurally similar and share mechanisms of action. Hence the possibility of a drug-drug interaction between rifabutin and methadone was evaluated in 24 methadone-maintained, former injecting drug users infected with the human immunodeficiency virus. The study was an open-label, drug-drug interaction and safety trial in which patients were followed for 15 days. Each patient received rifabutin 300 mg as a single dose concomitantly with their individualized methadone dosage. No significant differences in methadone peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, systemic clearance or renal clearance was observed in the presence of rifabutin. Seventy-five percent of the patients reported at least one symptom of narcotic withdrawal during the study, however, these symptoms were mild. A relationship between the development of narcotic withdrawal and methadone systemic exposure could not be established. Concurrent administration of rifabutin and methadone appeared to be safe in human immunodeficiency virus-infected injecting drug users maintained on stable doses of methadone and is not expected to produce any significant changes in the pharmacokinetics of methadone in these patients.
利福平是一种已知会降低美沙酮半衰期的药物，利福布汀与利福平结构相似且作用机制相同，均为利福霉素类药物。因此，研究人员在24名维持美沙酮治疗的、曾注射使用毒品且感染人类免疫缺陷病毒的患者中评估了利福布汀与美沙酮之间发生药物相互作用的可能性。该研究是一项开放标签的药物相互作用及安全性试验，对患者进行了15天的随访。每位患者在服用个体化美沙酮剂量的同时，单次服用300毫克利福布汀。在服用利福布汀的情况下，未观察到美沙酮的血浆峰浓度、达峰时间、血浆浓度-时间曲线下面积、全身清除率或肾脏清除率有显著差异。75%的患者在研究期间报告至少出现了一种阿片类药物戒断症状，不过这些症状较为轻微。无法确定阿片类药物戒断症状的出现与美沙酮全身暴露之间的关系。对于维持稳定剂量美沙酮治疗的感染人类免疫缺陷病毒的注射吸毒者，同时服用利福布汀和美沙酮似乎是安全的，预计不会对这些患者美沙酮的药代动力学产生任何显著影响。
