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

Robert L. Findling, Robert Goldman, Yu Yuan Chiu, Robert Silva, Fengbin Jin, Andrei Pikalov, Antony Loebel

Research output: Contribution to journalArticle

Abstract

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 Cmax, Tmax, and AUC0-24. Findings Exposure (Cmax and AUC0-24) 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 AUC0-24 and 0.70 ng/mL (0.52-0.87) for Cmax 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. ClinicalTrials.gov identifier: NCT01620060.

Original languageEnglish (US)
Pages (from-to)2788-2797
Number of pages10
JournalClinical therapeutics
Volume37
Issue number12
DOIs
StatePublished - Dec 1 2015

    Fingerprint

Keywords

  • bipolar I disorder
  • lurasidone
  • pediatric
  • pharmacokinetic
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this