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Clinical Pharmacokinetics of Sertraline

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Abstract

Sertraline is a naphthalenamine derivative with the predominant pharmacological action of inhibiting presynaptic reuptake of serotonin from the synaptic cleft. It was initially marketed for the treatment of major depressive disorder and is now approved for the management of panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder.

Sertraline is slowly absorbed following oral administration and undergoes extensive first-pass oxidation to form N-desmethyl-sertraline, a weakly active metabolite that accumulates to a greater concentration in plasma than the parent drug at steady state. Sertraline is eliminated from the body by other metabolic pathways to form a ketone and an alcohol, which are largely excreted renally as conjugates. The elimination half-life of sertraline ranges from 22–36 hours, and once-daily administration is therapeutically effective. Steady-state plasma concentrations vary widely, up to 15-fold, in patients receiving usual antidepressant dosages between 50 and 150 mg/day. However, only sparse data have been published that support useful correlations between sertraline plasma concentrations and therapeutic or adverse effects to justify therapeutic drug monitoring.

Sertraline has minimal inhibitory effects on the major cytochrome P450 enzymes, and few drug-drug interactions of clinical significance have been documented. Like other selective serotonin reuptake inhibitors, sertraline is well tolerated in therapeutic dosages and relatively safe in overdosage.

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  1. Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA

    C. Lindsay De Vane, Heidi L. Liston & John S. Markowitz

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  1. C. Lindsay De Vane
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De Vane, C.L., Liston, H.L. & Markowitz, J.S. Clinical Pharmacokinetics of Sertraline. Clin Pharmacokinet 41, 1247–1266 (2002). https://doi.org/10.2165/00003088-200241150-00002

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