Population pharmacokinetics of duloxetine in Japanese pediatric patients with major depressive disorder |
| |
| Affiliation: | 1. Clinical Pharmacology & Pharmacokinetics, Project Management Dept, Shionogi & Co, Ltd, Osaka, Japan;2. Pharmacokinetics/Pharmacodynamics & Pharmacometrics, Japan Drug Development & Medical Affairs, Eli Lilly Japan K.K, Kobe, Japan;1. Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg Universität Mainz, Mainz, Germany;2. Departamento de Farmacia, Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, 7820436, Chile;3. Max Planck Institute for Polymer Research, Mainz, Germany;4. University of Michigan, College of Pharmacy, Ann Arbor, MI, 48109, USA;5. Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, Uppsala, Sweden;1. Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan;2. Non-Clinical Regulatory Science, Applied Research & Operations, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan;3. Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan;4. Division of Risk Assessment, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kawasaki, 210-9501, Japan;1. Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan;2. School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan;3. National Institute of Health Sciences, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan;1. Pharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., Kobe, Japan;2. Clinical Pharmacology Department, Nippon Boehringer Ingelheim Co., Ltd., Kobe, Japan;3. Department of R&D Project Management and Development Strategies, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach, Germany;1. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China;2. Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children''s Medical Center, Guangzhou Medical University, Guangzhou, 510405, China;3. Department of Allergy and Clinical Immunology, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510405, China;4. Department of Pharmaceutics, School of Pharmacy, Ministry of Education, Fudan University & Key Laboratory of Smart Drug Delivery, Shanghai, 201203, China |
| |
| Abstract: | 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 identifierNCT03395353 |
| |
| Keywords: | Duloxetine Children and adolescents Japanese pediatric patients Population pharmacokinetics |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
