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Quetiapine: Preclinical Studies, Pharmacokinetics, Drug Interactions, and Dosing

Charles B. Nemeroff, MD, PhD; Becky Kinkead, PhD; and Jeffrey Goldstein, PhD

Published: December 31, 2002

Article Abstract

Quetiapine is a novel dibenzothiazepine atypical antipsychotic. Quetiapine shows affinity for variousneurotransmitter receptors including serotonin, dopamine, histamine, and adrenergic receptorsand has binding characteristics at the dopamine-2 receptor similar to those of clozapine. In animalmodels, the drug has a preclinical profile suggestive of antipsychotic activity with a reduced tendencyto cause extrapyramidal symptoms (EPS) and sustained prolactin elevation. For example, quetiapinealters neurotensin neurotransmission and c-fos expression in limbic but not motor brain regions. Thedrug also demonstrates clozapine-like activity in a range of behavioral and biochemical tests and maypossess neuroprotective properties. In humans, quetiapine exhibits linear pharmacokinetics with amean terminal half-life of 7 hours. The primary route of elimination of quetiapine is through hepaticmetabolism. Although not affected by smoking, alterations in quetiapine disposition due to age orhepatic impairment are manageable by appropriate dosage reduction. The optimal dosing range forquetiapine is 150 to 750 mg/day, and recent results suggest that once-daily dosing may be suitable forsome patients. Finally, imaging studies with positron emission tomography confirm significant differencesbetween quetiapine and typical antipsychotics that may be indicative of their differences inmechanism of action and propensity for producing EPS.

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