{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:42Z","timestamp":1786977042201,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["AT009101"],"award-info":[{"award-number":["AT009101"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007917","name":"Agricultural Research Service","doi-asserted-by":"publisher","award":["3092\u201051000\u2010062\u201001S"],"award-info":[{"award-number":["3092\u201051000\u2010062\u201001S"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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\u2009mg) in children and measured their effects on gut transit\/contractility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Children 7\u201312\u2009years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540\u2009mg or 900\u2009mg of oral enteric\u2010coated PMO. Blood was sampled over 24\u2009h to determine menthol PK. The WMC test was repeated while they took their respective dose (180\u2009mg thrice or 180\u2009mg five times daily) for a week.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010five children received 540\u2009mg, and 15 received 900\u2009mg (mean age 10.4\u2009\u00b1\u20091.1\u00a0years, 60% female). Peak plasma concentrations (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) were observed at approximately 2.5\u00a0h post\u2010dose. There was no evident dose effect for the apparent elimination rate constant, time of peak plasma concentration (\n                      <jats:italic>T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ),\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      , total plasma clearance, nor the apparent volume of distribution. Mean area under the plasma concentration\n                      <jats:italic>vs<\/jats:italic>\n                      . time curve (AUC) for the 900\u2009mg PMO dose cohort was approximately 1.5\u2010fold higher compared with the 540\u2009mg dose; the difference disappeared correcting for dose. Colonic and whole bowel transit time were significantly positively correlated with menthol AUC. The 900\u2009mg (\n                      <jats:italic>vs<\/jats:italic>\n                      . 540\u2009mg) dose decreased colonic (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002) and whole gut (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02) contraction frequency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The PK of menthol derived from PMO demonstrates apparent dose\u2010proportionality, and gut transit and contractility are associated with the systemic concentration of menthol.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70097","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:12:04Z","timestamp":1747721524000},"page":"2711-2724","source":"Crossref","is-referenced-by-count":2,"title":["Randomized trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain: 540\u2009mg\n                    <i>vs<\/i>\n                    . 900\u2009mg dose comparison"],"prefix":"10.1002","volume":"91","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 United States"},{"name":"Children's Nutrition Research Center  Houston TX United States"},{"name":"Texas Children's Hospital  Houston TX United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno 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