Meyer M C, Straughn A B, Lo M W, Schary W L, Whitney C C
J Clin Psychiatry. 1984 Sep;45(9 Pt 2):15-9.
Healthy male volunteers (N = 24) participated in a four-way crossover study to compare the rate and extent of absorption of naltrexone after administration of 50 mg tablets as 50, 100, and 200 mg doses and a 10 mg/ml reference syrup. A high-performance liquid chromatographic method was employed to measure naltrexone and 6-beta-naltrexol in plasma and urine. Compared to the syrup, the 50 mg tablets were absorbed more slowly but equally well. There was excellent linearity between the administered dose and the area under the plasma concentration-time profile, as well as total urinary recovery of both drug and metabolite. The mean half-lives for naltrexone and beta-naltrexol were approximately 4 and 12 hours, respectively. The fraction of drug reaching the systemic circulation was estimated to be 5% of the administered dose because of extensive first-pass metabolism. Less than 1% of the dose was excreted in the urine as naltrexone after 48 hours, while 25% was recovered as unconjugated beta-naltrexol. The renal clearance of naltrexone and beta-naltrexol was approximately 127 ml/min and 283 ml/min, respectively. The total systemic clearance for naltrexone was approximately 94 L/hr.
健康男性志愿者（N = 24）参与了一项四交叉研究，以比较服用50毫克片剂（剂量分别为50、100和200毫克）和10毫克/毫升参比糖浆后纳曲酮的吸收速率和吸收程度。采用高效液相色谱法测定血浆和尿液中的纳曲酮和6-β-纳曲醇。与糖浆相比，50毫克片剂吸收较慢，但吸收程度相同。给药剂量与血浆浓度-时间曲线下面积以及药物和代谢物的总尿回收率之间具有良好的线性关系。纳曲酮和β-纳曲醇的平均半衰期分别约为4小时和12小时。由于广泛的首过代谢，进入体循环的药物分数估计为给药剂量的5%。48小时后，作为纳曲酮经尿液排泄的剂量不到1%，而作为未结合β-纳曲醇回收的剂量为25%。纳曲酮和β-纳曲醇的肾清除率分别约为127毫升/分钟和283毫升/分钟。纳曲酮的总全身清除率约为94升/小时。
