Clinical Pharmacology & Pharmacokinetics, Shionogi & Co., Ltd., Osaka, Japan.
Clinical Pharmacology & Pharmacokinetics, Shionogi & Co., Ltd., Osaka, Japan.
J Pharm Sci. 2019 Sep;108(9):3112-3117. doi: 10.1016/j.xphs.2019.04.010. Epub 2019 Apr 16.
Baloxavir marboxil is a prodrug of baloxavir acid, an inhibitor of cap-dependent endonuclease, and suppresses the replication of influenza virus. The aim of this study was to investigate its pharmacokinetic characteristics in Japanese pediatrics. Population pharmacokinetic analysis was conducted for baloxavir acid with 328 plasma concentration data points in a clinical study of 107 Japanese pediatric influenza patients. The plasma baloxavir acid concentration profiles were well captured by a 2-compartment model including first-order absorption and lag time. Body weight was considered to be the most crucial covariate, which affects clearance and volume of distribution. The body weight-based dose regimen (10 mg for 10 kg to less than 20 kg pediatrics, 20 mg for 20 kg to less than 40 kg pediatrics, and 40 mg for at least 40 kg pediatrics) for Japanese pediatrics can provide comparable exposure to baloxavir acid to that for adults. In conclusion, the population pharmacokinetic model would be useful to comprehend the characteristics of baloxavir acid pharmacokinetics in pediatric patients.
巴洛沙韦马索利是巴洛沙韦酸的前药，是一种依赖于帽子的内切核酸酶抑制剂，可抑制流感病毒的复制。本研究旨在探讨其在日本儿科人群中的药代动力学特征。对 107 例日本儿科流感患者的临床研究中的 328 个血浆浓度数据点进行了巴洛沙韦酸的群体药代动力学分析。血浆巴洛沙韦酸浓度谱通过包括一级吸收和滞后时间的 2 室模型得到很好的描述。体重被认为是最重要的协变量，影响清除率和分布容积。对于日本儿科人群，基于体重的剂量方案（10 毫克用于 10 公斤至 20 公斤以下儿科患者，20 毫克用于 20 公斤至 40 公斤以下儿科患者，40 毫克用于至少 40 公斤儿科患者）可提供与成人相当的巴洛沙韦酸暴露量。总之，该群体药代动力学模型有助于了解儿科患者巴洛沙韦酸药代动力学特征。
