Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain

Authors: SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC); CHUMPITAZI, BRUNO - Children'S Nutrition Research Center (CNRC); ABDEL-RAHMAN, SUSAN - University Of Missouri; GARG, UTTAM - Children'S Mercy Hospital; MUSAAD, SALMA - Children'S Nutrition Research Center (CNRC); KEARNS, GREGORY - Texas Christian University

Submitted to: British Journal of Clinical Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2021
Publication Date: 9/16/2021
Citation: Shulman, R.J., Chumpitazi, B.P., Abdel-Rahman, S.M., Garg, U., Musaad, S., Kearns, G.L. 2021. Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain. British Journal Of Clinical Pharmacology. 88:1321-1333. https://doi.org/10.1111/bcp.15076.
DOI: https://doi.org/10.1111/bcp.15076

Interpretive Summary: Peppermint oil has been used for thousands of years to treat digestive problems. Despite this, how peppermint oil works is unclear. In this study, we measured how children metabolized different doses of peppermint oil after they took capsules containing peppermint oil. How fast food moved through the colon was related to the blood level of menthol – the major ingredient in peppermint oil. Similarly, how the muscles in the gut worked also was related to the blood level of peppermint oil. The results of this study will help guide proper use of peppermint oil in children.

Technical Abstract: 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 (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 = .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 AUClast (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.