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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Ascending-Dose Study of Noribogaine in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability
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Ascending-Dose Study of Noribogaine in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability

机译：健康志愿者中诺贝加因的升剂量研究：药代动力学，药效学，安全性和耐受性

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摘要

Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and C-max between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers.
机译：Noribogaine是天然存在的精神活性物质ibogaine的活性代谢产物，可能有助于抑制阿片类药物依赖性受试者的戒断症状。这项第一阶段研究的目的是评估诺贝加因的安全性，耐受性，药代动力学和药效动力学特征。在这项渐进的单剂量，安慰剂对照，随机，双盲，平行组研究中，对36名健康的无毒品男性志愿者进行了研究，其中4个队列（n = 9）接受了3、10、30或60 mg的口服剂量或与之匹配的安慰剂，可进行长达216小时的深入安全性和药代动力学评估，以及对μ阿片类激动剂的作用敏感的药效评估。 Noribogaine被迅速吸收，在口服给药后2-3小时达到峰值浓度，并在36.0 mg至60 mg的浓度时间曲线（AUC）和C-max下显示出剂量线性增加的面积。该药物逐渐被淘汰，各个剂量组的平均半衰期估计为28-49小时。表观分布量高（剂量组平均1417-3086 L）。在任何队列中均未发现安全性或耐受性问题。在瞳孔测定法或冷压试验中未发现μ阿片类激动剂的药效学作用。在健康志愿者中，单次口服剂量的诺贝加因3-60 mg安全且耐受性良好。

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