Pharmacology: Pharmacodynamics: Mechanism of Action: The exact mechanism by which Quetiapine exerts its antipsychotic effect is unknown. However, this effect may be mediated through antagonism of Dopamine type 2 (D2) and serotonin type 2 (5-HT2) receptors.
Quetiapine is an antagonist at serotonin 5-HT1A and 5-HT2, Dopamine D1 and D2, histamine H1 and adrenergic alpha1 and alpha2 receptors.
Quetiapine has no significant affinity for cholinergic muscarinic or benzodiazepine receptors. Drowsiness and orthostatic hypotension associated with the use of Quetiapine may be explained by its antagonism of histamine H1 and adrenergic alpha1 receptors, respectively.
Pharmacokinetics: Absorption: Rapidly and well-absorbed. Food increases peak plasma concentration (Cmax) and are under the plasma concentration-time curve (AUC) by 25% and 15%, respectively.
Distribution: Extensively distributed throughout the body, with an apparent volume distribution (VolD) of 10 ± 4 L/kg.
Protein binding: High (83%) to plasma proteins: Does not alter the binding of Warfarin or Diazepam to human serum albumin in vitro and Quetiapine binding is not altered in vitro by Warfarin or Diazepam.
Biotransformation: Extensively metabolized in the liver. Less than 5% of an orally administered dose is excreted unchanged. The major metabolic pathways are sulfoxidation, which in vitro studies indicate is mediated by the cytochrome P450 3A4 (CYP3A4) isoenzyme, and oxidation. The major metabolites of Quetiapine are inactive.
Half-life: Elimination: mean, about 6 to 7 hours.
Time to peak concentration: Peak plasma concentration is reached within 2 hours of dosing.
Elimination: Renal: Approximately 73% of an orally administered dose is excreted renally.
Fecal: Approximately 20% of an orally administered dose is excreted in feces.