静脉内丁丙诺啡和去甲丁丙诺啡在人体内的药代动力学。
Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans.
机构信息
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
出版信息
Drug Alcohol Depend. 2013 Aug 1;131(3):258-62. doi: 10.1016/j.drugalcdep.2012.11.014. Epub 2012 Dec 14.
BACKGROUND
Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine.
METHODS
Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography-tandem mass spectrometry with limits of quantitation of 0.1 μg/L.
RESULTS
Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3 ± 1.0, 44.5 ± 4.8, 85.2 ± 7.7, 124.6 ± 16.6, and 137.7 ± 18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10-15 min (3.7 ± 0.7 μg/L) after 16 mg IV administration.
CONCLUSIONS
Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2-16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg.
背景
处方舌下（SL）丁丙诺啡有时会被转移用于静脉内（IV）滥用，但尚无人类药代动力学数据可用于高剂量 IV 丁丙诺啡后。
方法
在 5 名健康的非依赖阿片类药物男性使用者中，以递增顺序（单盲，双盲）单次给予安慰剂或 2、4、8、12 或 16 mg IV 丁丙诺啡后，收集 72 小时的血浆。丁丙诺啡及其主要活性代谢物去甲丁丙诺啡通过液相色谱-串联质谱法进行定量，定量下限为 0.1 μg/L。
结果
10 分钟后检测到最大丁丙诺啡浓度（平均值±SE）：2、4、8、12、16 mg IV 分别为 19.3±1.0、44.5±4.8、85.2±7.7、124.6±16.6 和 137.7±18.8μg/L。最大去甲丁丙诺啡浓度在 16 mg IV 给药后 10-15 分钟出现（3.7±0.7μg/L）。
结论
丁丙诺啡浓度呈显著线性剂量依赖性增加，直至 12 mg IV 丁丙诺啡。因此，先前表现出的药效学上限效应（2-16 mg 之间）不是由于在此范围内的药代动力学适应引起的，尽管它们在剂量高于 12 mg 时可能起作用。
Zotero 插件