Victus Mechanism of Action



Amherst Lab


Full Prescribing Info
Pharmacology: Pharmacodynamics: Mechanism of Action: Quetiapine is an atypical antipsychotic. Quetiapine and its active human plasma metabolite, norquetiapine, interact with a broad range of neurotransmitter receptors in the brain. They exhibit affinity for brain serotonin 5-HT2 and dopamine D1 and D2. It is this combination of receptor antagonism with a higher selectivity of 5HT2 relative to D2 receptors which is believed to contribute to the clinical antipsychotic properties and less pronounced extrapyramidal symptoms (EPS) profile of quetiapine.
Quetiapine and norquetiapine also have high affinity at histaminergic and adrenergic α1 receptors, with a lower affinity at adrenergic α2 and serotonin 5HT1A receptors. Additionally, norquetiapine has high affinity for the norepinephrine transporter (NET).
Quetiapine has no appreciable affinity for β-adrenergic, δ-aminobutyric acid (GABA), benzodiazepine or muscarinic receptors.
Pharmacokinetics: Quetiapine is rapidly absorbed after oral administration, reaching peak plasma concentrations in 1.5 hours. The bioavailability of quetiapine is marginally affected by administration with food, with maximum plasma concentration (Cmax) and area under the plasma concentration time curve (AUC) values increased by 25% and 15%, respectively. Steady-state peak molar concentrations of the active metabolite norquetiapine are 35% of that observed for quetiapine.
Quetiapine is widely distributed throughout the body with an apparent volume of distribution of 10 ± 4 L/kg. It is approximately 83% bound to plasma proteins at therapeutic concentrations. The pharmacokinetics of quetiapine and norquetiapine are linear across the approved dosing range.
After a single oral dose of 14C-quetiapine, less than 1% of the administered dose was excreted as unchanged drug, indicating that quetiapine is highly metabolized. Quetiapine is extensively metabolized by the liver. The major metabolic pathways are sulfoxidation to the sulfoxide metabolite and oxidation to the parent acid metabolite; both metabolites are pharmacologically inactive. In vitro studies showed that CYP3A4 is the primary enzyme responsible for cytochrome P450 mediated metabolism of quetiapine. Norquetiapine is primarily formed and eliminated via CYP3A4.
Quetiapine and several of its metabolites (including norquetiapine) were found to be weak inhibitors of human cytochrome P450 1A2, 2C9, 2C19, 2D6 and 3A4 activities in vitro. In vitro CYP inhibition is observed only at concentrations approximately 5- to 50-fold higher than those observed at a dose range of 300 to 800 mg per day in humans.
The elimination half-lives of quetiapine and norquetiapine are approximately 7 and 12 hours, respectively. Quetiapine is mainly excreted as inactive metabolites with approximately 73% of the dose appearing in the urine and 20% in the feces. Less than 1% of the drug is excreted unchanged.
Special Population: Renal Impairment: Patients with severe renal impairment (CLCR= 10 to 30 mL/min) had a 25% lower mean oral clearance than normal subjects (CLCR>80 mL/min), but plasma quetiapine concentrations in patients with renal insufficiency were within the range of concentrations seen in normal subjects receiving the same dose. Dosage adjustment is not recommended.
Hepatic Impairment: Patients with hepatic impairment had a 30% lower mean quetiapine oral clearance than normal subjects. Higher plasma levels are expected in these patients since quetiapine is extensively metabolized by the liver. Dosage adjustment may be necessary.
Geriatrics (≥ 65 years old): Quetiapine oral clearance was reduced by 40% in elderly patients compared to young patients. Dosage adjustment may be necessary.
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