TY - JOUR
T1 - Pharmacokinetics and Tolerability of Lurasidone in Children and Adolescents with Psychiatric Disorders
AU - Findling, Robert L.
AU - Goldman, Robert
AU - Chiu, Yu Yuan
AU - Silva, Robert
AU - Jin, Fengbin
AU - Pikalov, Andrei
AU - Loebel, Antony
N1 - Funding Information:
The authors thank the investigators and patients who participated in the clinical trial summarized herein. The study sponsor, with consultative input from Dr. Findling, designed the study; and the study sponsor supervised the collection, analysis, and interpretation of the data. All authors participated in the development of the manuscript, and contributed to the decision for publication. Editorial and medical writing support was provided by Edward Schweizer, MD, Paladin Consulting Group, and was funded by Sunovion Pharmaceuticals Inc. Dr. Raymond Mankoski, Sunovion Pharmaceuticals Inc, contributed to medical writing and editing.
Publisher Copyright:
© 2015 The Authors. Published by Elsevier HS Journals, Inc. This is an open access article under the CC BY-NC-ND license.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - bipolar I disorder
KW - lurasidone
KW - pediatric
KW - pharmacokinetic
KW - schizophrenia
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U2 - 10.1016/j.clinthera.2015.11.001
DO - 10.1016/j.clinthera.2015.11.001
M3 - Article
C2 - 26631428
AN - SCOPUS:84951905176
SN - 0149-2918
VL - 37
SP - 2788
EP - 2797
JO - Clinical therapeutics
JF - Clinical therapeutics
IS - 12
ER -