Population Pharmacokinetic Modeling to Inform Sertraline Dosing Optimization in Patients with Depression

Stoiljković, Milan; Nikolić, Valentina; Ilić, Nebojša; Vujović, Marija; Popović, Dejan; Milovanović, Jasmina R.; Janković, Slobodan

doi:10.1159/000530084

Cited by 4 publications

(1 citation statement)

References 24 publications

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“…Based on our study of sertraline, we found that the mean dose-adjusted serum drug concentration (concentration/daily dose) was consistent with the AGNP guidelines, suggesting that pharmacokinetic differences between races are minimal. In a PPK study of sertraline, sertraline concentration data from 53 patients were used to find that N-desmethyl sertraline was a covariate affecting sertraline clearance [ 25 ]. In another, PPK study on sertraline and escitalopram, the CYP2C19 genotype was found to be a potential factor affecting sertraline clearance [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients

Zhang,

Guo,

Tan

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients

Zhang,

Guo,

Tan

et al. 2024

Heliyon

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Population Pharmacokinetics of Sertraline in Psychiatric and Substance Use Disorders

Castillo,

Garibay,

Segovia

et al. 2024

The Journal of Clinical Pharma

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This study aimed to characterize the population pharmacokinetics of sertraline in Mexican patients with psychiatric and substance use disorders. Fifty‐nine patients (13 to 76 years old) treated with doses of sertraline between 12.5 and 100 mg/day were included. Plasma sertraline concentrations were determined in blood samples and five of the main substances of abuse were determined by rapid tests in urine samples. Demographic, clinical, and pharmacogenetic factors were also evaluated. Population pharmacokinetic analysis was performed using NONMEM software with first‐order conditional estimation method. A one‐compartment model with proportional residual error adequately described the sertraline concentrations versus time. CYP2D6*2 polymorphism and CYP2C19 phenotypes significantly influenced sertraline clearance, which had a population mean value of 66 L/h in the final model. The absorption constant and volume of distribution were fixed at 0.855 1/h and 20.2 L/kg, respectively. The model explained 11.3% of the interindividual variability in sertraline clearance. The presence of the CYP2D6*2 polymorphism caused a 23.1% decrease in sertraline clearance, whereas patients with intermediate and poor phenotype of CYP2C19 showed 19.06% and 48.26% decreases in sertraline clearance, respectively. The model was internally validated by bootstrap and visual predictive check. Finally, stochastic simulations were performed to propose dosing regimens to achieve therapeutic levels that contribute to improving treatment response.

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A population pharmacokinetic model for sertraline in women during the perinatal period—A contribution from the ConcePTION project

Monfort,

Cardoso,

Eap

et al. 2024

Brit J Clinical Pharma

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AimsSertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability.MethodsPregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI‐Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk‐to‐plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model‐based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted.ResultsThirty‐eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 μg kg−1 after a 50 mg maternal daily dose, representing 0.95% of the weight‐adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL−1 after maternal daily doses between 25 and 150 mg.ConclusionsInfant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding.

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Population Pharmacokinetic Modeling to Inform Sertraline Dosing Optimization in Patients with Depression

Cited by 4 publications

References 24 publications

Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients

Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients

Population Pharmacokinetics of Sertraline in Psychiatric and Substance Use Disorders

A population pharmacokinetic model for sertraline in women during the perinatal period—A contribution from the ConcePTION project

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