Pharmacokinetics and Tolerability of Lurasidone in Children and Adolescents With Psychiatric Disorders

Purpose: The aim of this study was to evaluate the pharmacokinetic (PK) profile and tolerability of lurasidone in children and adolescents with a range of psychiatric disorders. Methods: This multicenter, open-label, single and multiple ascending-dose study of the PK profile of lurasidone (20, 40, 80, 120, and 160 mg/d) enrolled outpatients aged 6 to 17 years with a diagnosis of attention deficit/hyperactivity disorder, bipolar spectrum disorder, or other psychiatric disorder. Serial blood samples were collected for analysis of PK parameters, including C-max, T-max, and AUC(0-24). Findings: Exposure (C-max and AUC(0-24)) to lurasidone and its active metabolites showed linear increases across the entire dose range. Slope estimates (95% CI) across the dose range studied was 0.90 ng . h/mL (0.74-1.06) for AUC(0-24) and 0.70 ng/mL (0.52-0.87) for C-max on day 10 or 12. Lurasidone exposure, after multiple-dose administration in this child and adolescent population, was similar to exposure observed at steady state in adults. The effects of dose on exposure to the 3 active metabolites of lurasidone were linear and similar after the administration of single and multiple doses. Adverse events were qualitatively similar to those reported in adults. Discontinuations due to adverse events were dose related, with doses <120 mg/d being better tolerated than higher doses, especially in younger children. Implications: In this child and adolescent population, exposure parameters for lurasidone and its active metabolites were dose proportional in the range of 20 to 160 mg/d after the administration of single and multiple doses. These results suggest that lurasidone doses <120 mg/d were better tolerated compared with higher doses, especially in younger children. (C) 2015 The Authors. Published by Elsevier HS Journals, Inc.