A mechanistic population‐pharmacokinetic model was developed to predict oseltamivir exposures in neonates and infants accounting for physiological changes during the first 2 years of life. The model included data from 13 studies, comprising 436 subjects with normal renal function (317 pediatric subjects (≥ 38 weeks postmenstrual age (PMA), ≥ 13 days old) and 119 adult subjects < 40 years). Concentration–time profiles of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were characterized by a four‐compartment model, with absorption described by three additional compartments. Renal maturational changes were implemented by description of OC clearance with allometric function of weight and Hill function of PMA. Clearance of OC increased with weight up to 43 kg (allometric coefficient 0.75). Half the adult OC clearance was reached at a PMA of 45.6 weeks (95% confidence interval (CI) 41.6–49.6) with a Hill coefficient of 2.35 (95% CI 1.67–3.04). The model supports the European Union/United States‐approved 3 mg/kg twice‐daily oseltamivir dose for infants < 1 year (PMA ≥ 38 weeks) and allows prediction of exposures in preterm neonates.

中文翻译：

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Oseltamivir和Oseltamivir羧酸盐的机械种群药代动力学模型，说明生理变化以预测新生儿和婴儿的暴露。

建立了一种机械的人口-药代动力学模型，以预测新生儿和婴儿中的奥司他韦暴露，这解释了生命的头2年的生理变化。该模型包括来自13项研究的数据，包括436名肾功能正常的受试者（317名儿科受试者（月经年龄（PMA）≥38周，≥13天）和119名<40岁的成年受试者）。奥司他韦及其活性代谢物奥司他韦羧酸盐（OC）的浓度-时间曲线以四室模型为特征，吸收由另外三个室描述。通过描述OC清除率，体重的异度函数和PMA的Hill函数来实现肾脏的成熟变化。OC的清除量随重量增加而增加，达到43 kg（异速系数0.75）。PMA为45.6周（95％置信区间（CI）41.6–49.6）和Hill系数为2.35（95％CI 1.67–3.04）时，成人OC清除率达到了一半。该模型支持欧盟/美国批准的1岁以下（PMA≥38周）婴儿每日两次奥司他韦3 mg / kg每日两次剂量，并可以预测早产儿的暴露。