Pharmacology: Sertraline is a potent and specific inhibitor of neuronal serotonin (5 HT) uptake in vitro, which results in the potentiation of the effects of 5-HT in animals. It has only very weak effects on norepinephrine and dopamine neuronal reuptake. At clinical doses, Sertraline blocks the uptake of serotonin into human platelets. It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals.
Pharmacokinetics: Absorption: Sertraline exhibits dose proportional pharmacokinetics in the range of 50 to 200 mg. In man, following an oral once-daily dosage of 50 to 200 mg for 14 days, peak plasma concentrations of Sertraline occur at 4.5 to 8.4 hours after the daily administration of the drug. Food does not significantly change the bioavailability of Sertraline tablets.
Distribution: Approximately 98% of the circulating drug is bound to plasma proteins.
Biotransformation: Sertraline undergoes extensive first-pass hepatic metabolism.
Elimination: The mean half-life of Sertraline is approximately 26 hours (range 22-36 hours). Consistent with the terminal elimination half-life, there is an approximately two-fold accumulation up to steady state concentrations, which are achieved after one week of once-daily dosing. The half-life of N-desmethylsertraline is in the range of 62 to 104 hours. Sertraline and N-desmethylsertraline are both extensively metabolized in man and the resultant metabolites excreted in feces and urine in equal amounts. Only a small amount (<0.2%) of unchanged Sertraline is excreted in the urine.
Pharmacokinetics in specific patient groups: Adolescents and elderly: The pharmacokinetic profile in adolescents or elderly is not significantly different from that in adults between 18 and 65 years.
Liver function impairment: In patients with liver damage, the half life of Sertraline is prolonged and AUC is increased three fold.
Renal impairment: In patients with moderate-severe renal impairment, there was no significant accumulation of Sertraline.
Pharmacogenomics: Plasma levels of Sertraline were about 50% higher in poor metabolizers of CYP2C19 versus extensive metabolizers. The clinical meaning is not clear, and patients need to be titrated based on clinical response.