PMID- 28392509
OWN - NLM
STAT- MEDLINE
DCOM- 20170705
LR  - 20220328
IS  - 1347-5223 (Electronic)
IS  - 0009-2363 (Linking)
VI  - 65
IP  - 6
DP  - 2017 Jun 1
TI  - Bioequivalence and Pharmacokinetic Profiles of Agomelatine 25-mg Tablets in 
      Healthy Chinese Subjects: A Four-Way Replicate Crossover Study Demonstrating High 
      Intra- and Inter-Individual Variations.
PG  - 524-529
LID - 10.1248/cpb.c16-00866 [doi]
AB  - The present study was designed to assess the bioequivalence of two agomelatine 
      formulations (25-mg tablets) in healthy Chinese male subjects. This single-dose, 
      open-label, randomized, four-way replicate study with a 1-week washout period was 
      conducted in 60 healthy Chinese male volunteers under fasting conditions. Blood 
      samples were collected over a 12-h period after a single dose of the 25-mg 
      agomelatine test (T) formulation or a reference (R) formulation, and the drug 
      concentrations were assayed by liquid chromatography tandem mass spectrometry 
      (LC-MS/MS). Pharmacokinetic parameters were calculated using a non-compartmental 
      model. Bioequivalence between the formulations was assessed. Tolerability and 
      safety were monitored by physical examination, electrocardiogram (12-lead ECG), 
      clinical laboratory tests, and adverse events (AEs). A total of 56 out of 60 
      subjects completed the study. No AEs were observed. The values of maximum plasma 
      concentration (C(max)), maximum concentration (T(max)), area under curve 
      (AUC)(0-t) and t(1/2) were 12.032 ng/mL, 0.658 h, 12.637 ng.h/mL, and 0.813 h, 
      respectively, for the test formulation, and 10.891 ng/mL, 0.709 h, 
      11.572 ng.h/mL, and 0.96 h, respectively, for the reference formulation. The 
      intra-individual variability of C(max) and AUC(0-t) were 78.3 and 61.8%, 
      respectively. The inter-individual coefficients of variance (CVs) of C(max) and 
      AUC(0-t) were approximately 100%. The 90% confidence intervals for the ratio of 
      means for the log-transformed C(max) (97.7-124.9%), AUC(0-t) (98.2-118%), and 
      AUC(0-infinity) (97.8-117.2%) were within the guideline range of bioequivalence 
      (80-125%). The test and reference formulations of agomelatine met the regulatory 
      criteria for bioequivalence of the Chinese Food and Drug Administration. 
      Significant intra-individual and inter-individual variations were found.
FAU - Li, Cuiyun
AU  - Li C
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Xu, Jing
AU  - Xu J
AD  - Department of Neurology, The First Hospital of Jilin University.
FAU - Zheng, Yan
AU  - Zheng Y
AD  - Department of Geriatrics, The First Hospital of Jilin University.
FAU - Chen, Guiling
AU  - Chen G
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Wang, Jianmeng
AU  - Wang J
AD  - Department of Geriatrics, The First Hospital of Jilin University.
FAU - Ma, Liying
AU  - Ma L
AD  - The Second Hospital of Jilin.
FAU - Qiao, Yan
AU  - Qiao Y
AD  - Department of Clinical Laboratory, The Second Hospital of Jilin.
FAU - Niu, Junqi
AU  - Niu J
AD  - Department of Hepatology, The First Hospital of Jilin University.
FAU - Wu, Min
AU  - Wu M
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Li, Xiaojiiao
AU  - Li X
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Chen, Hong
AU  - Chen H
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Zhu, Xiaoxue
AU  - Zhu X
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Liu, Chengjiao
AU  - Liu C
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
FAU - Ding, Yanhua
AU  - Ding Y
AD  - Phase I Clinical Unit, China-Frontage USA, The First Hospital of Jilin 
      University.
LA  - eng
PT  - Journal Article
DEP - 20170408
PL  - Japan
TA  - Chem Pharm Bull (Tokyo)
JT  - Chemical & pharmaceutical bulletin
JID - 0377775
RN  - 0 (Acetamides)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Tablets)
RN  - 137R1N49AD (agomelatine)
SB  - IM
MH  - Acetamides/adverse effects/blood/*pharmacokinetics
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - China
MH  - Cross-Over Studies
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Hypnotics and Sedatives/adverse effects/blood/*pharmacokinetics
MH  - *Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
OTO - NOTNLM
OT  - agomelatine
OT  - bioequivalence
OT  - inter-individual variation
OT  - intra-individual
OT  - pharmacokinetic
EDAT- 2017/04/11 06:00
MHDA- 2017/07/06 06:00
CRDT- 2017/04/11 06:00
PHST- 2017/04/11 06:00 [pubmed]
PHST- 2017/07/06 06:00 [medline]
PHST- 2017/04/11 06:00 [entrez]
AID - 10.1248/cpb.c16-00866 [doi]
PST - ppublish
SO  - Chem Pharm Bull (Tokyo). 2017 Jun 1;65(6):524-529. doi: 10.1248/cpb.c16-00866. 
      Epub 2017 Apr 8.