Division of Clinical Pharmacology & Toxicology, Department of Paediatrics, Hospital for Sick Children, University of Toronto, , Toronto, Ontario, Canada.
Arch Dis Child. 2014 Mar;99(3):258-61. doi: 10.1136/archdischild-2013-305151. Epub 2013 Dec 20.
Oral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin.
A pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry.
Results showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%).
We conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.
在发展中国家，婴儿使用口服抗生素具有挑战性，因为通常无法获得液体制剂。然而，将药物的固体制剂溶解在水中会有引发胃肠道感染的风险。虽然母乳可能是一种潜在的载体，但没有证据表明溶解在母乳中的抗生素与溶解在水中的抗生素具有生物等效性。因此，我们比较了口服给予的抗生素阿莫西林在母乳中溶解与在水中溶解的药代动力学参数。
采用随机交叉设计，在 16 名健康成年志愿者中进行了一项药代动力学研究。将市售的阿莫西林混悬剂粉末溶解在母乳或水中，终浓度为 50mg/ml，在空腹状态下口服给予 10ml。采集时间点血样，并使用液相色谱-质谱法定量血浆中的阿莫西林。
结果表明，水基和乳基阿莫西林给药的药代动力学参数，包括曲线下面积、Cmax 和半衰期，均无显著差异。同时母乳给药与水给药这些参数比值的 90%置信区间在 89%和 116%之间，提示其生物等效（定义为 80%至 125%范围内）。
我们得出结论，以 50mg/ml 的浓度口服给予母乳中的阿莫西林可产生与溶解在水中的阿莫西林相当的药代动力学特征。阿莫西林与母乳之间的药物相互作用不太可能发生，这表明无需修改给药方案。
