Sertraline pharmacokinetics and dynamics in adolescents.
OBJECTIVE
To determine the pharmacokinetics of sertraline in adolescents and assess its effect on a surrogate marker of serotonin transport.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Axelson
David A
DA
University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA 15213, USA. axelsonda@msx.upmc.edu
Perel
James M
JM
Birmaher
Boris
B
Rudolph
George R
GR
Nuss
Sharon
S
Bridge
Jeffrey
J
Brent
David A
DA
D000293:Adolescent / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D020280:Sertraline / Q000493:pharmacokinetics*
D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline