Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Kiinamyllynkatu 4-8, Turku, Finland.
Eur J Clin Pharmacol. 2012 Jun;68(6):979-86. doi: 10.1007/s00228-012-1214-9.
We examined the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral S-ketamine.
A randomized crossover open-label study design with two phases at an interval of 4 weeks was conducted in 12 healthy volunteers. Grapefruit juice or water was ingested 200 ml t.i.d. for 5 days. An oral dose of 0.2 mg/kg of S-ketamine was ingested on day 5 with 150 ml grapefruit juice or water. Plasma concentrations of ketamine and norketamine were determined for 24 h, and pharmacodynamic variables were recorded for 12 h. Noncompartmental methods were used to calculate pharmacokinetic parameters.
Grapefruit juice increased the geometric mean value of the area under the plasma ketamine concentration-time curve(AUC0-∞) by 3.0-fold (range 2.4- to 3.6-fold; P<0.001), the peak plasma concentration (Cmax) by 2.1-fold (range 1.8- to 2.6-fold; P<0.001), and the elimination half-life by 24% (P<0.05) as compared to the water phase. The ratio of main metabolite norketamine to ketamine (AUCm/AUCp) was decreased by 57% (P<0.001) during the grapefruit phase.Self-rated relaxation was decreased (P<0.05) and the performance in the digit symbol substitution test was increased (P<0.05) after grapefruit juice, but other behavioral or analgesic effects were not affected.
Grapefruit juice significantly increased the plasma concentrations of oral ketamine in healthy volunteers.Dose reductions of ketamine should be considered when using oral ketamine concomitantly with grapefruit juice.
我们研究了柚子汁对口服 S-氯胺酮药代动力学和药效学的影响。
这是一项在 12 名健康志愿者中进行的为期 4 周的两阶段随机交叉开放标签研究设计。志愿者在 5 天内每天口服 200 毫升柚子汁或水，tid。在第 5 天，志愿者口服 0.2mg/kg 的 S-氯胺酮，同时摄入 150 毫升柚子汁或水。在 24 小时内测定氯胺酮和去甲氯胺酮的血浆浓度，并记录 12 小时的药效学变量。采用非房室模型法计算药代动力学参数。
与水相比，柚子汁使氯胺酮的 AUC0-∞几何均值增加了 3.0 倍（范围 2.4 至 3.6 倍；P<0.001），Cmax 增加了 2.1 倍（范围 1.8 至 2.6 倍；P<0.001），消除半衰期增加了 24%（P<0.05）。与水相比，主要代谢物去甲氯胺酮与氯胺酮的比值（AUCm/AUCp）降低了 57%（P<0.001）。在柚子汁阶段，志愿者的自我评估放松程度降低（P<0.05），数字符号替换测试的表现提高（P<0.05），但其他行为或镇痛作用不受影响。
柚子汁显著增加了健康志愿者口服氯胺酮的血浆浓度。当同时使用口服氯胺酮和柚子汁时，应考虑减少氯胺酮的剂量。
