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

Kearns GL, Chumpitazi BP, Abdel-Rahman SM, Garg U, Shulman RJ - BMJ Open (2015)

Bottom Line: 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%.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

No MeSH data available.


Related in: MedlinePlus

Mean (± 95% confidence interval) plasma concentration vs. time data for menthol in a cohort of six children with Irritable Bowel Syndrome given a single oral dose of peppermint oil containing approximately 83.0 mg of menthol [top panel] and individual plasma menthol concentration vs. time data [bottom panel].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4538270&req=5

BMJOPEN2015008375F1: Mean (± 95% confidence interval) plasma concentration vs. time data for menthol in a cohort of six children with Irritable Bowel Syndrome given a single oral dose of peppermint oil containing approximately 83.0 mg of menthol [top panel] and individual plasma menthol concentration vs. time data [bottom panel].

Mentions: The composite (mean±95% confidence limits) and individual plasma menthol concentration versus time data are shown in panels A and B of the figure 1, respectively. Considerable intersubject variability in the plasma concentration versus time profiles was apparent with all participants in the cohort. Individual PK parameters for menthol are provided in table 1. The time of appearance (Tmax) for apparent peak plasma concentrations (Cmax) ranged from 2.5 to 8 h following a lag time (Tlag) which ranged from 1.5 to 4 h. Absolute Cmax values ranged from 458 to 1056 ng/mL, which when corrected to a weight-adjusted menthol dose received by each child ranged from 255 to 470 ng/mL per 1 mg/kg (ie, an approximate 1.8-fold difference). The dose normalised systemic menthol exposure reflected by the area under the plasma concentration versus time curve (AUC per mg/kg dose) varied over an approximate twofold range (1464.1 to 2941.1 ng/mL×h). Given the marked delay in the appearance of menthol in plasma after a PMO dose, sufficient postpeak plasma concentrations to reliably estimate an apparent elimination rate constant (λz) and elimination half-life were not available in all participants. Consequently, the non-compartmental parameter mean residence time (MRT; a time representing elimination of approximately 60% of a given dose from the body) was determined using statistical moment theory and ranged from 6.4 to 9.4 h (table 1).


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

Kearns GL, Chumpitazi BP, Abdel-Rahman SM, Garg U, Shulman RJ - BMJ Open (2015)

Mean (± 95% confidence interval) plasma concentration vs. time data for menthol in a cohort of six children with Irritable Bowel Syndrome given a single oral dose of peppermint oil containing approximately 83.0 mg of menthol [top panel] and individual plasma menthol concentration vs. time data [bottom panel].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4538270&req=5

BMJOPEN2015008375F1: Mean (± 95% confidence interval) plasma concentration vs. time data for menthol in a cohort of six children with Irritable Bowel Syndrome given a single oral dose of peppermint oil containing approximately 83.0 mg of menthol [top panel] and individual plasma menthol concentration vs. time data [bottom panel].
Mentions: The composite (mean±95% confidence limits) and individual plasma menthol concentration versus time data are shown in panels A and B of the figure 1, respectively. Considerable intersubject variability in the plasma concentration versus time profiles was apparent with all participants in the cohort. Individual PK parameters for menthol are provided in table 1. The time of appearance (Tmax) for apparent peak plasma concentrations (Cmax) ranged from 2.5 to 8 h following a lag time (Tlag) which ranged from 1.5 to 4 h. Absolute Cmax values ranged from 458 to 1056 ng/mL, which when corrected to a weight-adjusted menthol dose received by each child ranged from 255 to 470 ng/mL per 1 mg/kg (ie, an approximate 1.8-fold difference). The dose normalised systemic menthol exposure reflected by the area under the plasma concentration versus time curve (AUC per mg/kg dose) varied over an approximate twofold range (1464.1 to 2941.1 ng/mL×h). Given the marked delay in the appearance of menthol in plasma after a PMO dose, sufficient postpeak plasma concentrations to reliably estimate an apparent elimination rate constant (λz) and elimination half-life were not available in all participants. Consequently, the non-compartmental parameter mean residence time (MRT; a time representing elimination of approximately 60% of a given dose from the body) was determined using statistical moment theory and ranged from 6.4 to 9.4 h (table 1).

Bottom Line: 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%.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

No MeSH data available.


Related in: MedlinePlus