Clinical Pharmacology & Pharmacokinetics, Project Management Dept, Shionogi & Co, Ltd, Osaka, Japan.
Clinical Pharmacology & Pharmacokinetics, Project Management Dept, Shionogi & Co, Ltd, Osaka, Japan.
Drug Metab Pharmacokinet. 2023 Aug;51:100496. doi: 10.1016/j.dmpk.2023.100496. Epub 2023 Feb 15.
The objectives of this analysis were to characterize the pharmacokinetics of duloxetine in Japanese pediatric patients aged 9-17 years with major depressive disorder (MDD) and to explore potential intrinsic factors affecting its pharmacokinetics. A population pharmacokinetic (PK) model was developed with plasma steady-state duloxetine concentrations from Japanese pediatric patients with MDD in an open-label long-term extension trial in Japan (ClinicalTrials.gov Identifier: NCT03395353). Duloxetine pharmacokinetics in Japanese pediatric patients was well described by a one-compartment model with first-order absorption. The population mean estimates of CL/F and V/F of duloxetine were 81.4 L/h and 1170 L, respectively. Patient intrinsic factors were assessed for their potential influence on duloxetine apparent clearance (CL/F). Only sex was identified as a statistically significant covariate of duloxetine CL/F. Duloxetine pharmacokinetic parameters and model-predicted duloxetine concentrations at steady state in the Japanese pediatric population were compared with those in Japanese adults. The mean duloxetine CL/F in pediatrics is slightly higher than adults, it is, however, expected that comparable steady-state duloxetine exposure in pediatric patients can be achieved with the approved dose regimen for adults. The population PK model provides useful information to understand the pharmacokinetic characteristics of duloxetine for Japanese pediatric patients with MDD. CLINICALTRIALS.GOV IDENTIFIER: NCT03395353.
本分析的目的是描述患有重度抑郁症（MDD）的 9-17 岁日本儿科患者的度洛西汀药代动力学特征，并探讨可能影响其药代动力学的内在因素。采用来自日本一项开放标签的长期扩展试验中 MDD 日本儿科患者的稳态度洛西汀血浆浓度，建立群体药代动力学（PK）模型（ClinicalTrials.gov 标识符：NCT03395353）。度洛西汀在日本儿科患者中的药代动力学特征通过具有一级吸收的单室模型得到很好的描述。度洛西汀的群体平均估计 CL/F 和 V/F 分别为 81.4 L/h 和 1170 L。评估了患者内在因素对度洛西汀表观清除率（CL/F）的潜在影响。只有性别被确定为度洛西汀 CL/F 的统计学显著协变量。比较了日本儿科人群中度洛西汀药代动力学参数和模型预测的稳态度洛西汀浓度与日本成年人的参数和浓度。儿科人群中的平均度洛西汀 CL/F 略高于成年人，但预计可以通过批准的成人剂量方案实现儿科患者稳态度洛西汀的可比暴露。群体 PK 模型提供了有用的信息，有助于了解日本 MDD 儿科患者度洛西汀的药代动力学特征。CLINICALTRIALS.GOV IDENTIFIER：NCT03395353。
