title: Pharmacokinetics and Tolerability of Lurasidone in Children and Adolescents With Psychiatric Disorders.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Johns Hopkins University, and Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, Marlborough, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldman
authors.affiliation: Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, Marlborough, Massachusetts.
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Chiu
authors.affiliation: Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, Marlborough, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Silva
authors.affiliation: Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, Marlborough, Massachusetts.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Jin
authors.affiliation: Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, Marlborough, Massachusetts.
authors.forename: Andrei
authors.initials: A
authors.lastname: Pikalov
authors.affiliation: Sunovion Pharmaceuticals Inc, Fort Lee, New Jersey, Marlborough, Massachusetts. Electronic address: antony.loebel@sunovion.com.
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D006801:Humans; D000069056:Lurasidone Hydrochloride / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D000069056:Lurasidone Hydrochloride
keywords: bipolar I disorder; lurasidone; pediatric; pharmacokinetic; schizophrenia