Population Pharmacokinetics of Sertraline in Healthy Subjects: a Model-Based Meta-analysis

Ali A. Alhadab, Richard C. Brundage

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Sertraline pharmacokinetics is poorly understood and highly variable due to large between-subject variability with inconsistent reports for oral bioavailability. The study objective was to characterize sertraline pharmacokinetics by developing and validating a sertraline population pharmacokinetic (PK) model in healthy subjects using published clinical PK data. We carried a systematic literature search in PubMed in October 2015 and identified 27 pharmacokinetic studies of sertraline conducted in healthy adult subjects and reported in the English language. Sixty mean plasma concentration-time profiles made of 748 plasma concentrations following IV, single, and multiple oral doses ranging from 5 to 400 mg were extracted and analyzed for dose proportionality by a log-linear model and fitted to a 2-compartment pharmacokinetic model in NONMEM using a model-based meta-analysis (MBMA) approach. After a single oral dose, sertraline Cmax and AUC increased with dose proportionally between 50 and 200 mg, and bioavailability increased nonlinearly with dose from 5 to 50 mg and plateaued afterwards while Tmax and t1/2 did not change with dose. Following multiple oral doses, Cmax and AUC increased proportionally with dose across the entire dose range (5–200 mg) while bioavailability, Tmax, and t1/2 remained constant with dose. Sertraline absorption was time-dependent and best described by a sigmoidal Emax function of time after dose. Study findings indicate that sertraline PK is linear in healthy adult subjects at doses ≥ 50 mg, and exposures were nonlinear only after single oral doses < 50 mg likely due to reduced bioavailability.

Original languageEnglish (US)
Article number73
JournalAAPS Journal
Issue number4
StatePublished - May 19 2020

Bibliographical note

Publisher Copyright:
© 2020, American Association of Pharmaceutical Scientists.


  • healthy subjects
  • meta-analysis
  • population pharmacokinetics
  • sertraline

PubMed: MeSH publication types

  • Journal Article
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review


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