Aurasert Mechanism of Action

Pharmacology: Pharmacodynamics: Setraline is a potent and selective inhibitor of neuronal serotonin (5-HT) reuptake. It has only a weak effect on Neuronal uptake of nor-epinephrine and dopamine. Setraline's inhibition of serotonin reuptake enhances serotonergic transmission.
In vitro studies have shown that sertraline has no significant affinity for adrenergic, muscarinic, cholinergic, gamma aminobutyric acid (GABA), dopaminergic, serotonergic (5HT1A, 5HT1B, 5HT2) histaminergic or benzodiazepine receptors.
Pharmacokinetics: The gastrointestinal absorption of setraline is slow but consistent. Sertraline undergoes extensive first-pass metabolism in the liver. The bioavailability is slightly increased if setraline is taken with food. Mean peak plasma concentrations of about 20-55 mcg/l occur between 4.5-8.4 hours after administration of a single 100mg dose. Sertraline is approximately 98% bound to plasma proteins. Both sertraline and its metabolites are extensively distributed into tissues. The metabolite n-desmethylsertraline exhibits only about 1/8 of its activity. It does not contribute to the antidepressant activity or toxicity of the parent compound. Both sertraline and its metabolite undergo oxidative deamination and subsequent reduction, hydroxylation and glucuronide conjugation. Only 0.2% of the unchanged drug is excreted through the kidneys. The elimination half-life of sertraline is 24 to 26 hours. The pharmacokinetics of sertraline in elderly patients is similar to younger adults.
Sertraline pharmacokinetics have been evaluated in a group of 61 pediatric patients (29 aged 6-12 years, 32 aged 13-17 years) with a DSM-III-R diagnosis of depression or obsessive-compulsive disorder. During 42 days of chronic sertraline dosing, sertraline was titrated upto 200mg/day and maintained at that dose for a minimum of 11 days. Relative to the adults, both the 6-12 year olds and 13-17 years old showed about 22% lower AUC (0-24 hours) and Cmax values when plasma concentration was adjusted for weight. These data suggest that paediatric patients metabolize sertraline with slightly greater efficiency in adults. Nevertheless, lower doses may be advisable for pediatric patients given their lower body weights, especially in very young patients, in order to avoid excessive plasma levels.