Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients

Abstract

Object: Sertraline is a first-line SSRI for the treatment of depression and has the same effectiveness along with a superior safety profile compared to other medications. There are few population pharmacokinetic (PPK) studies of sertraline and a lack of studies in the Chinese population. Therefore, we performed a PPK analysis of Chinese patients treated with sertraline to identify factors that can influence drug exposure. In addition, the dosing and discontinuation regimen of sertraline when applied to adolescents was explored. Methods: Sertraline serum drug concentration data were collected from 140 hospitalized patients to generate a sertraline PPK dataset, and data evaluation and examination of the effects of covariates on drug exposure in the final model were performed using nonlinear mixed-effects models (NONMEM) and first-order conditional estimation with interaction (FOCE-I). Examining rational medication administration and rational withdrawal of sertraline based on significant covariates and final modeling. Results: A one-compartment model with first-order absorption and elimination of sertraline was developed for Chinese patients with psychiatric disorders. Analysis of covariates revealed that age was a covariate that significantly affected sertraline CL/F (P < 0.01) and that sertraline clearance decreased progressively with aging, whereas other factors had no effect on CL/F and V/F of sertraline. In the age range of 11–79, there were 54 adolescent patients (about 1/3) aged 13–18 years, and the safe and effective optimal daily dose for adolescent patients based on the final model simulations was 50–250 mg/d. For adolescent patients, serum concentration fluctuations were moderate for OD doses of 50 mg and 100 mg, using a fixed dose-descent regimen. For patients with OD doses of 150–200 mg and BID doses of 100–200 mg, a more gradual decrease in serum concentration was achieved with a fixed dose interval of 7 or 14 days for 25 mg as the regimen of descent. Conclusions: To our knowledge, this may be the first PPK study of sertraline in Chinese patients. We found that age was an important factor affecting clearance in Chinese patients taking sertraline. Patients taking sertraline may be exposed to increased amounts of sertraline due to decreased clearance with increasing age. The rational dosing and safe discontinuation of sertraline in adolescent patients can be appropriately referenced to the results of the model simulation, thus providing assistance for individualized dosing in adolescents.

Keywords

• Sertraline
• Population pharmacokinetic
• Age
• Adolescents
• Discontinue the drug