Steady-state pharmacokinetic, safety, and tolerability profiles of quetiapine, norquetiapine, and other quetiapine metabolites in pediatric and adult patients with psychotic disorders.

Objective: The aim of this study was to investigate the steady-state pharmacokinetic, safety, and tolerability profiles of immediate-release quetiapine administered by similar dose-escalation regimens in pediatric and adult populations with psychotic or mood disorders. Methods: Pediatric patients aged 10-17 years were titrated to a quetiapine dose of 200 mg twice daily (b.i.d. on days 5-7, 400 mg b.i.d. on days 11-12, with a final 400-mg dose on day 13. In a separate trial, adult patients aged 18-45 years were titrated to a quetiapine dose of 200 mg b.i.d. on days 4-6, 400 mg b.i.d. on days 10-11, with a final 400-mg dose on day 12. Concentrations of quetiapine and three metabolites (quetiapine sulfoxide, 7-hydroxy quetiapine, and norquetiapine) were quantified in plasma and urine. Adverse events, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests were evaluated throughout the studies. Results: In both pediatric and adult populations, plasma concentrations of quetiapine and norquetiapine increased proportionately as the dose was escalated from 200 mg b.i.d. to 400 mg b.i.d. There were no age-related differences in the dose-normalized quetiapine plasma concentration-time curve (AUC(ss)) and maximum plasma concentration (C-SS,C-max). Quetiapine was rapidly absorbed after 200-mg and 400-mg doses in pediatric patients [median t(max) (time to maximum plasma concentration) 1.5 hours, both doses] and adult patients (median t(max) 1.0 hour and 1.2 hours, respectively). The mean quetiapine t(1/2) (terminal elimination half-life) was approximately 6 hours for pediatric and 5 hours for adult patients. Norquetiapine displayed a similar median t(max) and a longer t(1/2) compared with quetiapine. Quetiapine was well tolerated, with no serious adverse events and no unexpected events reported. Conclusion: Pediatric and adult populations demonstrated similar pharmacokinetic, safety, and tolerability profiles for quetiapine administered by dose escalation. The predictability in quetiapine concentration profiles for children aged 10 years to adults suggests that no dosage adjustment may be required when treating patients of these ages.