Randomized trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain: 540 mg vs. 900 mg dose comparison.

Abstract

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 mg five times daily) for a week.

Results: Twenty-five children received 540 mg, and 15 received 900 mg (mean age 10.4 ± 1.1 years, 60% female). Peak plasma concentrations (C_max) were observed at approximately 2.5 h post-dose. There was no evident dose effect for the apparent elimination rate constant, time of peak plasma concentration (T_max), C_max, total plasma clearance, nor the apparent volume of distribution. Mean area under the plasma concentration vs. time curve (AUC) for the 900 mg PMO dose cohort was approximately 1.5-fold higher compared with the 540 mg dose; the difference disappeared correcting for dose. Colonic and whole bowel transit time were significantly positively correlated with menthol AUC. The 900 mg (vs. 540 mg) dose decreased colonic (P = 0.002) and whole gut (P = 0.02) contraction frequency.

Conclusions: The PK of menthol derived from PMO demonstrates apparent dose-proportionality, and gut transit and contractility are associated with the systemic concentration of menthol.