RIFAMPIN-INDUCED METHADONE WITHDRAWAL
RIFAMPIN-INDUCED METHADONE WITHDRAWAL
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DOI：
10.1056/nejm197605132942008
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发表时间：
1976-01-01
影响因子：
158.5
通讯作者：
GIUSTI, LM
中科院分区：
文献类型：
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作者：
KREEK, MJ;GARFIELD, JW;GIUSTI, LM
六结核海洛因成瘾者谁开发严重戒断症状，而美沙酮和利福平进行了评估。美沙酮或利福平剂量和结核病分期之间无统计学差异。麻醉剂、巴比妥类药物、安非他明和镇静剂的尿液监测显示，研究期间没有患者摄入这些药物。在利福平治疗期间，除了当美沙酮血浆水平处于检测下限（0.01 μ g/ml）时，在口服美沙酮剂量后的每个时间点血浆美沙酮浓度始终较低（33-68%）（P < 0.001）。无论与利福平给药相关的研究顺序如何，血浆美沙酮浓度均降低。平均24小时尿中排泄的吡咯烷，美沙酮的主要代谢产物增加了150%，在利福平治疗期间研究的4例患者。停用和接受利福平治疗时，原型美沙酮的24小时粪便排泄量无一致变化。计算美沙酮的表观终末血浆半衰期。吡咯烷酮代谢物的血浆浓度降低和尿排泄增加表明利福平可能通过增强肝微粒体药物代谢酶活性发挥其作用。利福平治疗也可能改变美沙酮的分布。美沙酮血浆浓度的降低被这些患者出现的麻醉药戒断症状所掩盖。
Six tuberculous heroin addicts who developed severe withdrawal symptoms while on methadone and rifampin were evaluated. There was no statistically significant difference between methadone or rifampin dosage or stage of tuberculosis. Urine monitoring for narcotics, barbiturates, amphetamines and transquilizers, showed that no patients ingested these drugs during the study. During rifampin treatment, plasma methadone concentrations were consistently lower (33-68%) at each time point after oral methadone doses (P < 0.001), except when methadone plasma levels were at the lower limit of detection (0.01 .mu.g/ml). The reduction in plasma methadone concentration occurred regardless of the sequence of studies in relation to rifampin administration. Mean 24 h urinary excretion of pyrrolidine, a major metabolite of methadone increased 150% in 4 patients studied during rifampin treatment. There was no consistent changes in 24 h fecal excretion of unchanged methadone off and on rifampin treatment. The apparent terminal plasma half-life of methadone was calculated. The lowering of plasma concentrations and increased urinary excretion of the pyrrolidone metabolite suggest that rifampin might exert its effect by enhancing hepatic microsomal drug-metabolizing enzyme activities. Methadone distribution may also be altered by rifampin treatment. The lowering of methadone plasma levels was paralleled by the appearance of narcotic withdrawal symptoms in these patients.