Zsa Zsa Weerts

Chapter 6 122 Abstract Introduction 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. Methods In this randomized, double-blind, crossover study, subjects received 182 mg of either SI- PO or IC-PO in a crossover design with a >14 days washout period. Blood samples were collected to determine menthol-glucuronide concentrations. Results Eight healthy volunteers (50% female, median age 22) were included. The time to reach the maximum concentration (T max ) 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 lag ) was significantly longer with a median (IQR) of 225 (204-284) for IC-PO compared to 37 (6- 65) for SI-PO. The Area Under the menthol-glucuronide plasma concentration time Curves were significantly smaller with a median (IQR) of 2331μg*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. Conclusions IC-PO has a significantly delayed peak menthol-glucuronide concentration and T lag , 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.