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Systemic exposure to menthol following administration of peppermint oil to paediatric patients
  1. Gregory L Kearns1,2,3,
  2. Bruno Pedro Chumpitazi4,5,
  3. Susan M Abdel-Rahman1,3,
  4. Uttam Garg6,7,
  5. Robert J Shulman4,5,8
  1. 1Departments of Pediatrics, University of Missouri—Kansas City, Kansas City, Missouri, USA
  2. 2Departments of Pharmacology, University of Missouri—Kansas City, Kansas City, Missouri, USA
  3. 3Divisions of Pediatric Pharmacology, Medical Toxicology &Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA
  4. 4Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
  5. 5Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, Texas, USA
  6. 6Departments of Pathology, University of Missouri—Kansas City, Kansas City, Missouri, USA
  7. 7Clinical Laboratory Medicine, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA
  8. 8Children's Nutrition Research Center, Houston, Texas, USA
  1. Correspondence to Dr Gregory L Kearns; gkearns{at}


Objective Peppermint oil (PMO) has been used to treat abdominal ailments dating to ancient Egypt, Greece and Rome. Despite its increasing paediatric use, as in irritable bowel syndrome (IBS) treatment, the pharmacokinetics (PK) of menthol in children given PMO has not been explored.

Design and setting Single-site, exploratory pilot study of menthol PK following a single 187 mg dose of PMO. Subjects with paediatric Rome II defined (IBS; n=6, male and female, 7–15 years of age) were enrolled. Blood samples were obtained before PMO administration and at 10 discrete time points over a 12 h postdose period. Menthol was quantitated from plasma using a validated gas chromatography mass spectrometry technique. Menthol PK parameters were determined using a standard non-compartmental approach.

Results Following a dose of PMO, a substantial lag time (range 1–4 h) was seen in all subjects for the appearance of menthol which in turn, produced a delayed time of peak (Tmax=5.3±2.4 h) plasma concentration (Cmax=698.2±245.4 ng/mL). Tmax and Tlag were significantly more variable than the two exposure parameters; Cmax, mean residence time and total area under the curve (AUC=4039.7±583.8 ng/mL×h) which had a coefficient of variation of <20%.

Conclusions Delayed appearance of menthol in plasma after oral PMO administration in children is likely a formulation-specific event which, in IBS, could increase intestinal residence time of the active ingredient. Our data also demonstrate the feasibility of using menthol PK in children with IBS to support definitive studies of PMO dose–effect relationships.


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