Investigating Remedial Strategies for Missed or Delayed Dose of Sertraline in Chinese Adolescent Patients with Depressive Disorders via Population Pharmacokinetics Modeling and Simulation Approaches

Hui Xia,1,2,* Guowei Deng,1,2,* Fengtao Liang,3 Zi Zhang,1 Wanting Huang,1 Zhihao Guo,1 Qi Song,4 Yuguan Wen,1,2 Dewei Shang,1,2 Yaqian Tan1,2 1Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Obstetrics, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, People’s Republic of China; 4Department of Pharmacy, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaqian Tan, Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, Mingxin Road 36, Liwan District, Guangzhou, 510370, People’s Republic of China, Email [email protected] Dewei Shang, Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, Mingxin Road 36, Liwan District, Guangzhou, 510370, People’s Republic of China, Email [email protected]: Sertraline is a commonly used medication for adolescent patients with depression, and missed or delayed dose has been frequently observed during long-term treatment. However, little is known about the remedial strategies for missed or delayed dose of sertraline. Hence, we designed the remedial strategies of different missed dosage scenarios based on population pharmacokinetics (PPK) model simulation, aiming to provide medication guidance to Chinese adolescent depressive patients.Methods: A total of 221 sertraline concentration monitoring data were collected from 103 sertraline-treated adolescent patients with depression. Data analysis was performed using nonlinear mixed-effects model, and situations of different missed doses were simulated in the sertraline PPK model, including one single missed dose and double/triple missed doses under different therapeutic dosages.Results: A one-compartment model without covariates was established to characterize the PPK of sertraline in adolescent patients with depression. Population typical values of sertraline clearance and apparent distribution volume were 65.8 L/h and 1570 L, respectively. Our simulation results revealed that when adolescent patients missed or delayed sertraline administration, the scheduled dose should be administered immediately. Additionally, our results suggested that the dose of the next remedial time should be adjusted according to the duration of the delay and the frequency of missed doses.Conclusion: In this study, we developed remedy strategies for missed or delayed dosing of sertraline in Chinese adolescents with depression based on our PPK model simulations. These findings may provide valuable clinical guidance for sertraline treatment in this population. Keywords: sertraline, adolescents, missed or delayed dose, population pharmacokinetics, modeling and simulation