{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:05:51Z","timestamp":1781622351952,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK56338"],"award-info":[{"award-number":["P30 DK56338"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["58\u20103092\u20100\u2010001"],"award-info":[{"award-number":["58\u20103092\u20100\u2010001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AT009101"],"award-info":[{"award-number":["AT009101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty children ages 7\u201312\u2009years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540\u2009mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24\u2009hours. They then took their respective dose of PMO (180\u2009mg once, 180\u2009mg twice or 180\u2009mg thrice daily) for 1 week during which time the WMC test was repeated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Evaluable area under the plasma concentration <jats:italic>vs<\/jats:italic>. time curve (AUC<jats:sub>last<\/jats:sub>) data were available in 29 of 30 participants. A direct linear relationship (apparent dose\u2010proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half\u2010life 2.1, 3.5 and 4.6\u00a0hours for the 180, 360 and 540\u2009mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUC<jats:sub>last<\/jats:sub> (<jats:italic>P\u2009=<\/jats:italic>\u00a0.003); transit time in other regions was not affected. In contrast, stomach, small bowel and whole gut (but not colonic) contractility positively correlated with menthol AUC<jats:sub>last<\/jats:sub> (<jats:italic>P\u2009&lt;<\/jats:italic>\u00a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose\u2010proportionality. A higher dose of PMO may be needed to achieve maximal gut response. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link> NCT03295747.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15076","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T07:47:05Z","timestamp":1631778425000},"page":"1321-1333","source":"Crossref","is-referenced-by-count":14,"title":["Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2385-0991","authenticated-orcid":false,"given":"Robert J.","family":"Shulman","sequence":"first","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston TX USA"},{"name":"Children's Nutrition Research Center Baylor College of Medicine  Houston TX 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