Kearns Gregory L, Chumpitazi Bruno Pedro, Abdel-Rahman Susan M, Garg Uttam, Shulman Robert J
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.
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, Texas, USA.
BMJ Open. 2015 Aug 12;5(8):e008375. doi: 10.1136/bmjopen-2015-008375.
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.
目的:薄荷油(PMO)自古埃及、希腊和罗马时代起就被用于治疗腹部疾病。尽管其在儿科的应用日益增加,如用于治疗肠易激综合征(IBS),但尚未对给予PMO的儿童体内薄荷醇的药代动力学(PK)进行研究。 设计与背景:对单次服用187 mg PMO后薄荷醇的PK进行单中心探索性初步研究。纳入符合儿科罗马II标准(IBS;n = 6,男女皆有,7 - 15岁)的受试者。在服用PMO前及给药后12小时内的10个离散时间点采集血样。采用经过验证的气相色谱 - 质谱技术对血浆中的薄荷醇进行定量。使用标准的非房室方法确定薄荷醇的PK参数。 结果:服用一剂PMO后,所有受试者体内薄荷醇的出现均有明显的滞后时间(范围为1 - 4小时),这反过来导致血浆浓度达到峰值的时间延迟(Tmax = 5.3 ± 2.4小时)(Cmax = 698.2 ± 245.4 ng/mL)。Tmax和Tlag的变异性显著高于另外两个暴露参数;Cmax、平均驻留时间和曲线下总面积(AUC = 4039.7 ± 583.8 ng/mL×h),其变异系数<20%。 结论:儿童口服PMO后血浆中薄荷醇的延迟出现可能是特定剂型的事件,在IBS中,这可能会增加活性成分在肠道内的驻留时间。我们的数据还证明了在患有IBS的儿童中使用薄荷醇PK来支持PMO剂量 - 效应关系的确定性研究的可行性。
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