Teoh S K, Mendelson J H, Mello N K, Kuehnle J, Sintavanarong P, Rhoades E M
Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, Massachusetts 02178.
J Clin Psychopharmacol. 1993 Apr;13(2):87-99.
Recent preclinical and clinical studies suggest that buprenorphine, an opioid mixed agonist-antagonist, may be useful for the treatment of dual dependence on cocaine and opiates. This report describes an inpatient clinical evaluation of the safety of buprenorphine alone and in combination with single doses of cocaine and morphine. Twenty subjects with a DSM-III-R diagnosis of concurrent cocaine and opioid dependence were randomly assigned to maintenance treatment with single daily doses of 4 or 8 mg of sublingual buprenorphine for 21 days. Side effects and vital signs were evaluated every day once every 8 hours and for 2 hours after daily buprenorphine administration. The physiologic effects of a single-blind challenge dose of cocaine (30 mg intravenously), morphine (10 mg intravenously), and intravenous saline placebo were measured before and during buprenorphine maintenance. Before buprenorphine maintenance, subjects underwent methadone detoxification followed by a 9-day drug-free period. Three baseline single-blind challenge dose studies were conducted on study days 7, 8, and 9 during the drug-free period. Cardiovascular responses to cocaine and to morphine were equivalent under drug-free and buprenorphine maintenance conditions. Respiration and temperature changes in response to cocaine were also equivalent before and during buprenorphine maintenance. Respiratory rates were slightly lower after morphine administration during maintenance on 8 mg of buprenorphine, but this was not statistically significant. Mild opioid agonist-like side effects were reported during buprenorphine induction and maintenance. These included headache, sedation, nasal discharge, abdominal discomfort, and anxiety. Most opioid agonist side effects decreased within 12 to 14 days. An electrocardiogram and blood chemistry measures were normal before and during buprenorphine maintenance. These data suggest that daily maintenance on buprenorphine is not associated with adverse side effects or toxic interactions with a single acute dose of intravenous cocaine or morphine.
近期的临床前和临床研究表明，丁丙诺啡，一种阿片类混合激动剂-拮抗剂，可能对治疗可卡因和阿片类药物双重依赖有用。本报告描述了对丁丙诺啡单独使用以及与单剂量可卡因和吗啡联合使用的安全性进行的住院临床评估。20名符合DSM-III-R诊断标准的同时患有可卡因和阿片类药物依赖的受试者被随机分配接受每日单剂量4毫克或8毫克舌下丁丙诺啡维持治疗21天。每天每8小时评估一次副作用和生命体征，并在每日丁丙诺啡给药后2小时进行评估。在丁丙诺啡维持治疗前和治疗期间，测量单次盲法挑战剂量的可卡因（静脉注射30毫克）、吗啡（静脉注射10毫克）和静脉注射生理盐水安慰剂的生理效应。在丁丙诺啡维持治疗前，受试者先进行美沙酮脱毒，随后有9天的戒毒期。在戒毒期的第7、8和9天进行了三项基线单次盲法挑战剂量研究。在戒毒和丁丙诺啡维持治疗条件下，对可卡因和吗啡的心血管反应相当。在丁丙诺啡维持治疗前和治疗期间，对可卡因的呼吸和体温变化也相当。在8毫克丁丙诺啡维持治疗期间，吗啡给药后呼吸频率略低，但无统计学意义。在丁丙诺啡诱导和维持治疗期间报告了轻微的阿片类激动剂样副作用。这些副作用包括头痛、镇静、流涕、腹部不适和焦虑。大多数阿片类激动剂副作用在12至14天内减轻。在丁丙诺啡维持治疗前和治疗期间，心电图和血液化学指标均正常。这些数据表明，每日使用丁丙诺啡维持治疗与单次急性静脉注射可卡因或吗啡无不良副作用或毒性相互作用。
