Q-Pin Mechanism of Action



Full Prescribing Info
Pharmacology: Mechanism action: Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, Norquetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and Norquetiapine exhibits affinity for brain serotonin (5HT2) and dopamine D1 and D2 receptors. It is this combination of receptor antagonism with a higher selectivity for 5HT2 relative to dopamine D2 receptors which is believed to contribute to the antipsychotic properties and low extrapyramidal side effect (EPS) liability of Quetiapine compared to typical antispychotics. Quetiapine has no affinity for the Norepinephrine transporter (NET) and low affinity for the serotonin 5HT1A receptor, whereas Norquetiapine has high affinity for both. Inhibition of NET and partial agonist action at 5HT1A sites by Norquetiapine may contribute to Quetiapine's therapeutic efficacy as an antidepressant. Quetiapine and Norquetiapine have high affinity at histaminergic and adrenergic alpha1 receptors and moderate affinity at adrenergic alpha2 receptors. Quetiapine also has low or no affinity for muscarinic receptors, while Norquetiapine has moderate to high affinity for several muscarinic receptor subtypes, which may explain anti-cholinergic (muscarinic) effects.
Pharmacodynamics: Quetiapine is active in tests for antipsychotic activity, such as conditioned avoidance. It also blocks the action of dopamine agonists, measured either behaviourally or electrophysiologically, and elevates dopamine metabolite concentrations, a neurochemical index of dopamine D2 receptor blockade.
The extent to which the Norquetiapine metabolite contributes to the pharmacological activity of Quetiapine in humans is not known.
Pharmacokinetics: This study was designed as a randomized, single blind, two period, single dose, cross-over study with one week washout period in 26 healthy subjects under fasting condition. The study was conducted following an oral administration of one tablet 25 mg of the test drug or one tablet 25 mg of the reference drug.
Based on the pharmacokinetic parameters of Quetiapine (N = 26), mean ± SD for Test Drug and Reference Drug showed: Cmax values were 98.89 (40.67) and 92.19 (39.24) ng.mL-1, respectively; AUCt values were 358.76 (151.38) and 362.66 (155.63) h.ng.mL-1, respectively; AUCinf values were 369.53 (156.42) and 374.79 (163.36) h.ng.mL-1, respectively; Tmax values were 0.75 (0.33 - 2.00) and 0.75 (0.50 - 1.50) hours, respectively; T1/2 values were 3.90 (1.27) and 4.18 (1.54) hours, respectively.
Results from bioequivalence study for Test Drug and Reference Drug were as following: 90.00% Confidence Intervals of geometric means ratio of the two bioavailability parameters of Quetiapine were 98.71 - 117.86% for Cmax and 94.37 - 103.75% for AUCt. Intra subject CV (%) of Cmax and AUCt for Quetiapine were 18.63 and 9.85%, respectively.
Conclusion: These results showed that 25 mg Quetiapine film coated tablet was bioequivalent to the reference product.
Special populations: Gender: The kinetics of Quetiapine do not differ between men and women.
Elderly: The mean clearance of Quetiapine in the elderly is lower than that seen in adults aged 18 to 65 years.
Renal impairment: The mean plasma clearance of Quetiapine was reduced in subjects with severe renal impairment, but the individual clearance values are within the range for normal subjects.
Hepatic impairment: As Quetiapine is extensively metabolised by the liver, elevated plasma levels are expected in the population with hepatic impairment. Dose adjustments may be necessary in these patients (see DOSAGE & ADMINISTRATION).
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