Systemic exposure to menthol following administration of peppermint oil to paediatric patients.
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.


METHODS
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.
Departments of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri, USA Departments of Pharmacology, University of Missouri-Kansas City, Kansas City, Missouri, USA Divisions of Pediatric Pharmacology, Medical Toxicology &Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
Gregory L
GL
Kearns
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, Texas, USA.
Bruno Pedro
BP
Chumpitazi
Departments of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri, USA Divisions of Pediatric Pharmacology, Medical Toxicology &Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
Susan M
SM
Abdel-Rahman
Departments of Pathology, University of Missouri-Kansas City, Kansas City, Missouri, USA Clinical Laboratory Medicine, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
Uttam
U
Garg
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, Texas, USA Children's Nutrition Research Center, Houston, Texas, USA.
Robert J
RJ
Shulman
D000284:Administration, Oral; D000293:Adolescent; D000932:Antiemetics / Q000008:administration & dosage*; D019540:Area Under Curve; D002648:Child; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008297:Male; D036142:Mentha piperita; D008610:Menthol / Q000097:blood*; D010865:Pilot Projects; D010938:Plant Oils / Q000008:administration & dosage*
D000932:Antiemetics; D010938:Plant Oils; D008610:Menthol; C015424:peppermint oil
PAEDIATRICS; THERAPEUTICS