Bell James, Shearer James, Ryan Anni, Graham Robert, Korompay Kristy, Rizzo Suzanne, Sindhusake Doungkamol, Somogyi Andrew A
The Langton Centre, Sydney, Australia.
Exp Clin Psychopharmacol. 2009 Jun;17(3):146-53. doi: 10.1037/a0016302.
Methadone is an effective therapy for heroin addiction, but the public health benefits are compromised by diversion and injection of prescribed methadone. Combination with naloxone is one way to reduce the risk of diversion and injection. Two studies were conducted. The first ascertained the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral methadone-naloxone in a 50:1 ratio compared with methadone. The second study investigated the effectiveness of intramuscularly injected methadone-naloxone in precipitating withdrawal in methadone-maintained subjects. The first double-blind, crossover study randomized 10 stable methadone-maintained subjects equally to receive either methadone-naloxone or methadone over two alternate 14 day periods. In the second study, 5 subjects received intramuscular injections of methadone-naloxone before their scheduled methadone dose. Oral methadone-naloxone in a 50:1 ratio appeared to be well tolerated, although a taste difference between the preparations may have compromised blinding. There were no significant differences between methadone and methadone-naloxone in objective and subjective opioid withdrawal signs, and trough and peak plasma concentrations. Methadone-naloxone in a 50:1 ratio intramuscularly precipitated mild to moderate signs of opioid withdrawal in 4 out of 5 subjects whereas a 5th subject who did not experience withdrawal at a lower dose refused higher dose challenges. Withdrawal symptoms peaked 15 to 30 minutes postchallenge and returned to baseline levels at 60 minutes. Methadone-naloxone in 50:1 ratio has the pharmacological properties to be a useful combination product for treatment of heroin addiction with reduced risk of injection.
美沙酮是治疗海洛因成瘾的有效疗法，但由于处方美沙酮的转移和注射，其公共卫生效益受到损害。与纳洛酮联合使用是降低转移和注射风险的一种方法。进行了两项研究。第一项研究确定了口服美沙酮 - 纳洛酮（比例为50:1）与美沙酮相比的安全性、耐受性、药代动力学和药效学。第二项研究调查了肌肉注射美沙酮 - 纳洛酮在促使接受美沙酮维持治疗的受试者戒断方面的有效性。第一项双盲交叉研究将10名稳定的接受美沙酮维持治疗的受试者平均随机分为两组，在两个交替的14天期间分别接受美沙酮 - 纳洛酮或美沙酮治疗。在第二项研究中，5名受试者在预定的美沙酮剂量之前接受了肌肉注射美沙酮 - 纳洛酮。比例为50:1的口服美沙酮 - 纳洛酮似乎耐受性良好，尽管制剂之间的味道差异可能影响了盲法。在客观和主观的阿片类药物戒断体征以及谷值和峰值血浆浓度方面，美沙酮和美沙酮 - 纳洛酮之间没有显著差异。比例为50:1的肌肉注射美沙酮 - 纳洛酮使5名受试者中的4名出现了轻度至中度的阿片类药物戒断体征，而第5名受试者在较低剂量时未出现戒断反应，拒绝了更高剂量的挑战。戒断症状在注射后15至30分钟达到峰值，并在60分钟时恢复到基线水平。比例为50:1的美沙酮 - 纳洛酮具有药理学特性，有望成为一种有用的联合产品，用于治疗海洛因成瘾，同时降低注射风险。
