Open label, three period, single sequence, study of 5, 25, 50 mg sertraline pharmacokinetics in healthy male Korean volunteers

Acute hemodynamic effects of a selective serotonin reuptake inhibitor in postural tachycardia syndrome: A randomized, crossover trial

“…Sertraline is a rapidly absorbed SSRI with peak concentrations at 4 hours with a 50mg dose (Park et al, 2011). In this trial, patients with POTS were given sertraline hydrochloride 50mg (American Health Packaging, Columbus, OH) and placebo (“Cebocaps”; Forest Pharmaceuticals, New York, NY) in a randomized crossover fashion on separate days.…”

“…These “proof-of-concept” drug trials were started in the morning at least 2 h after an early, light breakfast (to avoid acute hemodynamic effects from eating) in a post-void state. Sertraline is a rapidly absorbed SSRI with peak concentrations at 4 h with a 50mg dose (Park et al, 2011). In this trial, patients with POTS were given sertraline hydrochloride 50mg (American Health Packaging, Columbus, OH) and placebo (“Cebocaps”; Forest Pharmaceuticals, New York, NY) in a randomized crossover fashion on separate days.…”

“…Our primary end point was the standing HR 4 h after study drug administration. The 4-h time point was chosen because the peak plasma concentration of sertraline occurs 4 h after dosing (Park et al, 2011). The null hypothesis was that the standing HR would not be statistically different between sertraline and placebo.…”

PharmGKB summary: sertraline pathway, pharmacokinetics

“…Sertraline is slowly absorbed, with peak concentrations (C max ) occurring at 4-10 hours following ingestion, and has a half-life of 24-32 hours in children, adolescents and adults [11][12][13][14][15][16][17][18][19][20]. The therapeutic concentration range for sertraline has not been well established, but has been proposed to be 10-150 ng/mL [21].…”

“…There is a large interindividual variability in plasma concentrations between patients taking the same dose of sertraline, which may be partially due to variable expression of CYP3A4/5, discussed in the Metabolism section below [2,6] and genetic variation in CYP2C19, discussed in the Pharmacogenomics section [27]. This variability contributes to the weak relationship between the dose and plasma sertraline concentrations [15,26]. Although some studies have found a relationship between serum concentrations of sertraline and the magnitude of clinical effect on patients [28,29], other research has failed to replicate this association [23,30].…”