Randomised Trial: Peppermint Oil (Menthol) Pharmacokinetics in Children and Effects on Gut Motility in Children with Functional Abdominal Pain

Aims 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 three dose levels in children and determine their effects on gut motility and transit. Methods Thirty children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately one 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 one week during which time the WMC test was repeated. Results Evaluable area under the plasma concentration vs. time curve (AUClast ) 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 AUClast (P=0.003); transit time in other regions were not affected. In contrast, stomach, small bowel, and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P Conclusions 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.