Division of Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands.
Adv Ther. 2018 Nov;35(11):1965-1978. doi: 10.1007/s12325-018-0802-1. Epub 2018 Oct 4.
Peppermint oil (PO) has been shown to reduce abdominal pain in patients with irritable bowel syndrome (IBS). PO is assumed to induce intestinal smooth muscle relaxation and desensitization of nociceptive nerve afferents. To increase colonic PO concentration, an ileocolonic release peppermint oil (IC-PO) capsule has been developed. The aim of this study was to compare pharmacokinetic parameters of the currently available small intestinal release PO (SI-PO) and the novel IC-PO.
In this randomized, double-blind, crossover study, subjects received 182 mg of either SI-PO or IC-PO in a crossover design with a washout period of more than 14 days. Blood samples were collected to determine menthol glucuronide concentrations.
Eight healthy volunteers (50% female, median age 22) were included. The time to reach the maximum concentration (T) of IC-PO was significantly longer compared to SI-PO with a median (IQR) of 360 (360-405) versus 180 (120-180) min. The lag time (T) was significantly longer with a median (IQR) of 225 (204-284) for IC-PO compared to 37 (6-65) min for SI-PO. The areas under the menthol glucuronide plasma concentration-time curves were significantly smaller with a median (IQR) of 2331 μg h/L (2006-2510) for IC-PO compared to 2623 μg h/L (2471-2920) for SI-PO. No significant differences were found in peak concentrations and elimination half-lives.
IC-PO has a significantly delayed peak menthol glucuronide concentration and T, both pointing to the release of PO in the more distal part of the intestine. This may enhance therapeutic efficacy as it results in increased exposure of colonic mucosal afferents to the PO. A randomized controlled trial investigating the efficacy of SI and IC-PO in IBS is currently ongoing.
ClinicalTrials.gov identifier, NCT02291445, EudraCT database 2014-004195-32.
薄荷油（PO）已被证明可减轻肠易激综合征（IBS）患者的腹痛。薄荷油被认为可诱导肠平滑肌松弛和伤害感受传入神经的脱敏。为了增加结肠中 PO 的浓度，开发了一种回肠结肠释放薄荷油（IC-PO）胶囊。本研究旨在比较目前可用的小肠释放 PO（SI-PO）和新型 IC-PO 的药代动力学参数。
在这项随机、双盲、交叉研究中，受试者以交叉设计接受 182mg 的 SI-PO 或 IC-PO，洗脱期超过 14 天。采集血样以确定薄荷脑葡萄糖醛酸苷浓度。
纳入 8 名健康志愿者（50%为女性，中位年龄 22 岁）。IC-PO 的达峰时间（T）明显长于 SI-PO，中位数（IQR）分别为 360（360-405）和 180（120-180）分钟。IC-PO 的滞后时间（T）也明显长，中位数（IQR）为 225（204-284）分钟，而 SI-PO 为 37（6-65）分钟。IC-PO 的薄荷脑葡萄糖醛酸苷血浆浓度-时间曲线下面积明显小于 SI-PO，中位数（IQR）分别为 2331μg·h/L（2006-2510）和 2623μg·h/L（2471-2920）。峰浓度和消除半衰期无显著差异。
IC-PO 的薄荷脑葡萄糖醛酸苷峰浓度和 T 均显著延迟，这表明 PO 在肠的更远端释放。这可能会增强治疗效果，因为它会增加结肠黏膜传入神经对 PO 的暴露。目前正在进行一项随机对照试验，以研究 SI 和 IC-PO 在 IBS 中的疗效。
ClinicalTrials.gov 标识符，NCT02291445，EudraCT 数据库 2014-004195-32。
