PMID- 28695535
OWN - NLM
STAT- MEDLINE
DCOM- 20180528
LR  - 20221207
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 37
IP  - 9
DP  - 2017 Sep
TI  - Single- and Multiple-Dose Pharmacokinetics, Safety and Tolerability of Lurasidone 
      in Healthy Chinese Subjects.
PG  - 861-871
LID - 10.1007/s40261-017-0546-8 [doi]
AB  - BACKGROUND AND OBJECTIVE: The pharmacokinetics of lurasidone have been studied in 
      healthy Japanese and Caucasian subjects, but not in Chinese subjects. The 
      objective of this study was to evaluate the pharmacokinetics, safety, and 
      tolerability of oral lurasidone in healthy Chinese subjects. METHODS: This 
      single-center, randomized, parallel-group, placebo-controlled, and double-blind 
      study evaluated the pharmacokinetics, safety, and tolerability of oral lurasidone 
      administered as a single dose (20, 40, and 80 mg) and multiple doses for 5 days 
      (40 mg administered once daily) in healthy Chinese subjects. Serum lurasidone and 
      its metabolites were quantified using high-performance liquid chromatography-mass 
      spectrometry. Pharmacokinetic parameters for lurasidone and its metabolites were 
      calculated using non-compartmental analysis of WinNonlin((R)) version 6.2. Safety 
      analyses were recorded using physical examinations, vital signs, 
      electrocardiogram, and clinical laboratory tests. RESULTS: Serum concentrations 
      of lurasidone reached maximum concentration (C (max)) within 1.0-3.0 h after each 
      single dose, and then decreased biphasically, with a mean half-life (t ((1/2))) from 
      18.1 to 25.5 h over the dose range of 20-80 mg. The area under the 
      concentration-time curve (AUC) and C (max) values increased approximately dose 
      proportionally. Lurasidone steady state was achieved after 5 days of daily dosing 
      and the accumulation index of the AUC during a dosage interval (AUC(tau)) was 1.25, 
      smaller than theoretical cumulative coefficient (1.76). Similar results were 
      observed for the metabolites (ID-14283, ID-14326, and ID-11614). No severe 
      adverse events (AEs) were observed in the single- or multiple-dose studies and no 
      subject discontinued from the study due to AEs. The most common reported AEs were 
      somnolence, increased blood prolactin, and restlessness, with a higher rate as 
      dose increased. CONCLUSION: Lurasidone was safe and well-tolerated in healthy 
      Chinese subjects, following single doses in the range of 20 to 80 mg and multiple 
      doses of 40 mg/day for 5 days. Linear increase in lurasidone C (max) and AUC 
      values were seen following single doses from 20 to 80 mg. There was no unexpected 
      accumulation after multiple administrations of lurasidone at 40 mg/day, and the 
      pharmacokinetic characteristics were consistent with the conclusion obtained in 
      the previous studies. TRIAL REGISTRATION: Clinicaltrials.gov identifiers 
      NCT02174510 and NCT02174523.
FAU - Hu, Chaoying
AU  - Hu C
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai 
      Rd.(M), Shanghai, 200031, China.
FAU - Wang, Yijun
AU  - Wang Y
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai 
      Rd.(M), Shanghai, 200031, China.
FAU - Song, Rong
AU  - Song R
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai 
      Rd.(M), Shanghai, 200031, China.
FAU - Yu, Chen
AU  - Yu C
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai 
      Rd.(M), Shanghai, 200031, China.
FAU - Luo, Xiaoyan
AU  - Luo X
AD  - Sumitomo Pharmaceuticals (Suzhou) Co. Ltd., Beijing, China.
FAU - Jia, Jingying
AU  - Jia J
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, No. 966, Huaihai 
      Rd.(M), Shanghai, 200031, China. jyjia@shxh-centerlab.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT02174510
SI  - ClinicalTrials.gov/NCT02174523
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - O0P4I5851I (Lurasidone Hydrochloride)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - *Asian People
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Half-Life
MH  - Humans
MH  - Lurasidone Hydrochloride/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Male
MH  - Young Adult
EDAT- 2017/07/12 06:00
MHDA- 2018/05/29 06:00
CRDT- 2017/07/12 06:00
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2018/05/29 06:00 [medline]
PHST- 2017/07/12 06:00 [entrez]
AID - 10.1007/s40261-017-0546-8 [pii]
AID - 10.1007/s40261-017-0546-8 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2017 Sep;37(9):861-871. doi: 10.1007/s40261-017-0546-8.