Abstract
To determine the pharmacokinetics of sertraline in adolescents and assess its effect on a surrogate marker of serotonin transport. Pharmacokinetic parameters of a single 50-mg dose of sertraline were determined in 10 adolescents. Steady-state withdrawal kinetics were determined in 12 adolescents taking 50 mg/day and in 6 adolescents taking 100 to 150 mg/day. Platelet serotonin reuptake was measured before and after 2 weeks of daily 50-mg dosing. The mean steady-state half-life of 50 mg was significantly shorter (15.3 +/- 3.5 hours) than the single-dose half-life (26.7 +/- 5.2 hours; t = 6.4, p < .001) and the steady-state half-life at 100 to 150 mg/day (20.4 +/- 3.4 hours; t = 2.9, p = .01). Platelet serotonin reuptake was inhibited by 61 +/- 15% after approximately 2 weeks of sertraline 50 mg/day. The half-life of sertraline 50 mg becomes significantly shorter from the initial dose to steady-state, and many adolescents may benefit from twice-per-day dosing. The steady-state half-life increases as the dose increases. The moderate levels of platelet reuptake inhibition at 50 mg/day indicate that most adolescents may need sertraline doses higher than 50 mg/day to attain a therapeutic response.
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