Ferrari A, Bertolotti M, Dell'Utri A, Avico U, Sternieri E
Dipartimento di Medicina Interna, Università di Modena, Italy.
Drug Alcohol Depend. 1998 Nov 1;52(3):211-20. doi: 10.1016/s0376-8716(98)00098-2.
The pharmacokinetics of naltrexone have been scarcely explored in patients during chronic treatment despite the observation that the pharmacological effect of the drug is related to its plasma concentrations. In this study we investigated the time course of serum levels of naltrexone and its active metabolite, 6 beta-naltrexol, in 13 heroin addicts (3 F, 10 M; age 22-32 years) in the 24 h after 100 mg of naltrexone orally. Six patients were studied once, at different times during chronic treatment, whereas in seven patients the study was done at the beginning and after 1 month of naltrexone treatment. Four of these patients also repeated the study after 3 months of naltrexone treatment. Serum naltrexone and 6 beta-naltrexol were assayed by GLC with a nitrogen-phosphorus detector. Our results showed large differences among patients in serum naltrexone and 6 beta-naltrexol levels. On the other hand, there were no differences in serum time course of both substances in the same patient over 3 months. Peak levels and AUCs of naltrexone were lower than those of 6 beta-naltrexol in ten addicts and higher than those of the metabolite in three patients. No significant differences in the apparent half-lives of the two drugs were detected among groups. These data are consistent with the occurrence of a decreased first-pass metabolism of naltrexone in three patients leading to a larger availability of an oral dose. The increased bioavailability of the drug is not very important for opioid receptor antagonist activity but may play a role in naltrexone treatment safety.
尽管观察到纳曲酮的药理作用与其血浆浓度有关，但在慢性治疗期间，很少有研究探索纳曲酮在患者体内的药代动力学。在本研究中，我们调查了13名海洛因成瘾者（3名女性，10名男性；年龄22 - 32岁）口服100毫克纳曲酮后24小时内血清中纳曲酮及其活性代谢物6β-纳曲醇的时间进程。6名患者在慢性治疗的不同时间进行了一次研究，而7名患者在纳曲酮治疗开始时和治疗1个月后进行了研究。其中4名患者在纳曲酮治疗3个月后也重复了该研究。血清纳曲酮和6β-纳曲醇通过带有氮磷检测器的气相色谱法进行测定。我们的结果显示，患者之间血清纳曲酮和6β-纳曲醇水平存在很大差异。另一方面，同一患者在3个月内两种物质的血清时间进程没有差异。在10名成瘾者中，纳曲酮的峰值水平和AUC低于6β-纳曲醇，在3名患者中高于代谢物。各组之间两种药物的表观半衰期没有显著差异。这些数据与3名患者中纳曲酮首过代谢降低导致口服剂量可用性增加的情况一致。药物生物利用度的增加对阿片受体拮抗剂活性不是非常重要，但可能在纳曲酮治疗安全性中起作用。
