Kaiko R F, Grandy R P, Reder R F, Goldenheim P D, Sackler R S
Medical Department, Purdue Frederick Company, Norwalk, CT 06850-3590, USA.
J Clin Pharmacol. 1995 May;35(5):499-504. doi: 10.1002/j.1552-4604.1995.tb04094.x.
Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets. Morphine effects were blocked by three 100-mg doses of naltrexone. The first dose of naltrexone was given 24 hours before MSC dosing, followed by a second dose at the time of MSC dosing and a third dose 24 hours after MSC administration. Compared with two 100-mg MSC tablets, the 200-mg tablet was 96% bioavailable (90% confidence interval, 88.14-105.74%). The 90% confidence intervals for mean Cmax and AUC0-24 for one 200-mg MSC tablet were within +/- 20% of the Cmax and AUC0-24 of two 100-mg tablets, indicating the two dosage forms are bioequivalent. Single 200-mg doses of MSC given with the naltrexone blockade were generally well tolerated, and adverse effects were similar to those reported for naltrexone alone and for lower doses of morphine without naltrexone. Naltrexone proved safe and effective in blocking the effects of controlled-release morphine, permitting bioequivalence studies of a high dose of morphine in normal volunteers.
23名接受硫酸吗啡（美施康定）联合纳曲酮治疗的正常志愿者完成了本次随机、分析性盲法、双向交叉对照研究，比较了1片200毫克口服控释硫酸吗啡片与2片100毫克美施康定片的生物利用度。吗啡的作用被3次100毫克剂量的纳曲酮阻断。纳曲酮的第一剂在美施康定给药前24小时服用，第二剂在美施康定给药时服用，第三剂在美施康定给药后24小时服用。与2片100毫克美施康定片相比，200毫克片剂的生物利用度为96%（90%置信区间，88.14 - 105.74%）。1片200毫克美施康定片的平均Cmax和AUC0 - 24的90%置信区间在2片100毫克片剂的Cmax和AUC0 - 24的±20%范围内，表明两种剂型生物等效。在纳曲酮阻断作用下给予单剂量200毫克美施康定，一般耐受性良好，不良反应与单独使用纳曲酮以及未使用纳曲酮的较低剂量吗啡所报告的相似。纳曲酮被证明在阻断控释吗啡的作用方面安全有效，从而能够在正常志愿者中进行高剂量吗啡的生物等效性研究。
