Oo Charles, Hill George, Dorr Albert, Liu Baolian, Boellner Samuel, Ward Penelope
Roche Global Development, Nutley, NJ, USA.
Eur J Clin Pharmacol. 2003 Sep;59(5-6):411-5. doi: 10.1007/s00228-003-0639-6. Epub 2003 Aug 9.
The prodrug oseltamivir has been shown to be efficacious and safe for the treatment of influenza for patients 1 year of age or older; however, pharmacokinetic information was lacking for children below 5 years of age. This study was conducted to assess the metabolic and excretory capacity of oseltamivir and its active carboxylate metabolite in young children.
Twelve healthy children aged 1-5 years received a single oral suspension dose of oseltamivir (45 mg for 3-5 years, 30 mg for 1-2 years). Plasma and urine concentrations of oseltamivir and the carboxylate were determined by means of liquid chromatography/tandem mass spectrometry.
Mean peak plasma concentration and area under the plasma concentration-time curve values normalized to milligram per kilogram oseltamivir dose in the 1- to 2-year group are lower than those in the 3- to 5-year group. Mean body weight normalized oral clearance of oseltamivir and its carboxylate in younger subjects aged 1-2 years (259 ml/min/kg and 12.2 ml/min/kg) were, respectively, 52% and 30% higher than those in older subjects aged 3-5 years (170 ml/min/kg and 9.4 ml/min/kg).
The results demonstrate that infants as young as 1 year old can metabolize and excrete oseltamivir efficiently. The data derived from this study provide the starting dose of oseltamivir for further investigation in an efficacy study among influenza-infected infants less than 1 year of age.
前体药物奥司他韦已被证明对1岁及以上的流感患者治疗有效且安全；然而，5岁以下儿童的药代动力学信息尚缺。本研究旨在评估奥司他韦及其活性羧酸代谢物在幼儿中的代谢和排泄能力。
12名1至5岁的健康儿童单次口服奥司他韦混悬液（3至5岁服用45毫克，1至2岁服用30毫克）。采用液相色谱/串联质谱法测定血浆和尿液中奥司他韦及其羧酸代谢物的浓度。
1至2岁组中，以每千克奥司他韦剂量计算的血浆平均峰浓度和血浆浓度-时间曲线下面积值低于3至5岁组。1至2岁较年幼受试者中奥司他韦及其羧酸代谢物的平均体重标准化口服清除率（分别为259毫升/分钟/千克和12.2毫升/分钟/千克）比3至5岁较年长受试者（分别为170毫升/分钟/千克和9.4毫升/分钟/千克）分别高52%和30%。
结果表明，年仅1岁的婴儿能够有效地代谢和排泄奥司他韦。本研究所得数据为在小于1岁的流感感染婴儿中进行疗效研究提供了奥司他韦的起始剂量，以供进一步研究。
