title: Population pharmacokinetic modeling of quetiapine after administration of seroquel and seroquel XR formulations to Western and Chinese patients with schizophrenia, schizoaffective disorder, or bipolar disorder.
abstract: A population model describing quetiapine pharmacokinetics (PK) in Western and Chinese patients following oral administration of immediate-release (IR) and extended-release (XR) formulations was developed using plasma concentrations in 127 patients from 5 studies with quetiapine IR and/or XR in Western patients and 1 study with quetiapine XR in Chinese patients. A 1-compartmental model with first-order absorption and first-order elimination adequately described the quetiapine PK. The typical apparent volume of distribution and elimination rate constant of quetiapine were 574 L and 0.12 h(-) (1) , respectively. The estimated population absorption rate constants were 1.46 and 0.10 h(-1) for quetiapine IR and XR, respectively. Covariate analysis revealed that race was not a significant covariate influencing the PK of quetiapine. Simulation conducted with the final quetiapine population PK model predicted that the administration of a 200-mg twice-daily dose of quetiapine IR in Chinese patients would achieve a steady-state AUC (AUCss ) ± standard deviation of 3087 ± 1480 ng · h/mL, which is in close agreement with the reported value (3538 ± 1728 ng · h/mL). The model also predicted that once-daily administration of 300 mg quetiapine IR or XR would achieve similar exposure in terms of AUCss in Chinese patients.
authors.affiliation: Quantitative Clinical Pharmacology, AstraZeneca LP, Waltham, MA, USA.
authors.forename: Diansong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Quantitative Clinical Pharmacology, AstraZeneca LP, Waltham, MA, USA.
authors.forename: Khanh H
authors.initials: KH
authors.lastname: Bui
authors.affiliation: Quantitative Clinical Pharmacology, AstraZeneca LP, Waltham, MA, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: Quantitative Clinical Pharmacology, AstraZeneca LP, Waltham, MA, USA.
authors.forename: Nidal
authors.initials: N
authors.lastname: Al-Huniti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People; D001714:Bipolar Disorder / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011618:Psychotic Disorders / Q000378:metabolism*; D000069348:Quetiapine Fumarate / Q000097:blood / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D000069348:Quetiapine Fumarate
keywords: Chinese; Quetiapine; Western