Variability in Sertraline Pharmacokinetics in Routine Clinical Practice: Influence of Sex, Age, Body Weight, Smoking, and Co-Medication

Abstract

Objectives

To investigate the influence of sex, age, body weight, smoking habits, and co-medications on sertraline pharmacokinetics in a routine clinical setting.

Methods

This retrospective observational study analyzed 177 predominantly inpatient therapeutic drug monitoring records from 101 patients receiving sertraline as monotherapy or polytherapy. Pharmacokinetic parameters—serum concentrations (CSER), concentration-to-dose ratio (CDR), weight-normalized CDR (CDR/kg), apparent clearance (CL/F), and metabolite-to-parent ratio (N-SER/SER)—were compared across subgroups defined by sex, age (< 18; 18–65; > 65 years), BMI, smoking, and co-medications. To address the nonindependence of repeated measurements, analyses were complemented using linear mixed-effects models and a sensitivity analysis restricted to one observation per patient.

Results

Descriptive analyses suggested higher CDR/kg in males and higher CSER in elderly patients. After accounting for within-patient clustering, the increase in CDR/kg across BMI categories remained the most consistent finding, likely reflecting mathematical normalization. The higher CSER observed in elderly patients persisted in the mixed-effects model but not in the sensitivity analysis, although the direction of effect remained consistent. Sex-related differences were not robust after adjustment and were largely attributable to body weight. Smoking showed no measurable effect. Among co-medications, carbamazepine showed the most consistent pharmacokinetic signal, whereas other findings were less consistent.

Conclusion

Elderly age may contribute to higher sertraline concentrations; however, its effect appears modest after accounting for clustering. Sex differences are largely explained by body weight, and smoking does not appear to influence pharmacokinetics. Carbamazepine showed a consistent induction pattern, whereas other co-medication findings should be considered exploratory.