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.
