Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
Br J Clin Pharmacol. 2022 Mar;88(3):1321-1333. doi: 10.1111/bcp.15076. Epub 2021 Oct 19.
Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.
Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice or 180 mg thrice daily) for 1 week during which time the WMC test was repeated.
Evaluable area under the plasma concentration vs. time curve (AUC ) data were available in 29 of 30 participants. A direct linear relationship (apparent dose-proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half-life 2.1, 3.5 and 4.6 hours for the 180, 360 and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUC (P = .003); transit time in other regions was not affected. In contrast, stomach, small bowel and whole gut (but not colonic) contractility positively correlated with menthol AUC (P < .05).
Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose-proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.
薄荷醇是薄荷油（PMO）中的有效成分，有关其药代动力学和药效动力学的信息知之甚少。我们的目的是研究 3 个剂量水平的薄荷醇在儿童体内的药代动力学，并确定其对肠道动力和转运的影响。
30 名 7-12 岁患有功能性腹痛的儿童接受无线动力胶囊（WMC）检测。大约 1 周后，他们被随机分为 180、360 或 540mg 的肠溶 PMO（每组 10 名参与者）。通过 24 小时的血液采样来确定薄荷醇的药代动力学。然后，他们在 1 周内服用各自剂量的 PMO（180mg 一次、180mg 两次或 180mg 三次每日），在此期间重复进行 WMC 测试。
29 名 30 名参与者中可评估的血浆浓度-时间曲线下面积（AUC）数据。PMO 剂量与薄荷醇系统暴露之间存在直接线性关系（系统薄荷醇暴露的表观剂量比例），180、360 和 540mg 剂量的平均消除半衰期分别为 2.1、3.5 和 4.6 小时。WMC 技术问题导致所有参与者的完整运动数据都无法获得。结肠转运时间与 AUC 呈反比（P = .003）；其他区域的转运时间不受影响。相反，胃、小肠和整个肠道（但不包括结肠）的收缩性与薄荷醇 AUC 呈正相关（P < .05）。
PMO 衍生的薄荷醇的药代动力学和药效动力学表现出明显的剂量比例关系。可能需要更高剂量的 PMO 才能达到最大的肠道反应。www.clinicaltrials.gov NCT03295747。
