PMID- 33189559
OWN - NLM
STAT- MEDLINE
DCOM- 20210824
LR  - 20210824
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 35
IP  - 6
DP  - 2020 Dec
TI  - Pharmacokinetics, safety and metabolite profiling of minesapride, a novel 5-HT(4) 
      receptor partial agonist, in healthy elderly and young subjects.
PG  - 563-570
LID - S1347-4367(20)30418-3 [pii]
LID - 10.1016/j.dmpk.2020.09.005 [doi]
AB  - Minesapride is a novel 5-hydroxytryptamine 4 (5-HT(4)) receptor partial agonist 
      that is expected to show efficacy in patients with irritable bowel syndrome with 
      predominant constipation and functional constipation. An open-label study was 
      conducted to evaluate pharmacokinetics (PK) and safety of minesapride. Japanese 
      subjects, 12 elderly and 12 young, received a single oral dose of minesapride 
      40 mg/day in the fasted state. Metabolite profiles were also investigated in this 
      clinical study and in an in vitro study using cryopreserved hepatocytes. Clinical 
      results showed that minesapride was rapidly absorbed (C(max): 2302.1 ng/mL in the 
      elderly group, 2117.5 ng/mL in the young group), and the plasma concentration 
      then decreased with half-life of approximately 7 h. There were no notable PK 
      differences between elderly and young groups. No serious adverse events (AEs) 
      were observed. The only AE that occurred in 2 or more subjects was diarrhea. 
      Metabolite profiles in plasma and urine were similar between elderly and young 
      groups. No major metabolites exceeded 10% of unchanged minesapride, and results 
      of the in vitro study suggested that there were no human-specific metabolites. 
      From the viewpoints of PK and metabolite profiling, no dose adjustment of 
      minesapride is warranted in elderly population without renal or hepatic 
      impairment.
CI  - Copyright (c) 2020 The Japanese Society for the Study of Xenobiotics. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Hamatani, Tatsuto
AU  - Hamatani T
AD  - Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., 
      Ltd., Tokyo, Japan. Electronic address: tatsuto-hamatani@ds-pharma.co.jp.
FAU - Shibue, Yuta
AU  - Shibue Y
AD  - Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., 
      Ltd., Tokyo, Japan.
FAU - Sawada, Naoyuki
AU  - Sawada N
AD  - Preclinical Research Unit, Research Division, Sumitomo Dainippon Pharma Co., 
      Ltd., Osaka, Japan.
FAU - Takagaki, Takeshi
AU  - Takagaki T
AD  - Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., 
      Ltd., Tokyo, Japan.
FAU - Hashimoto, Masayo
AU  - Hashimoto M
AD  - Preclinical Research Unit, Research Division, Sumitomo Dainippon Pharma Co., 
      Ltd., Osaka, Japan.
FAU - Nakada, Yosuke
AU  - Nakada Y
AD  - Data Science, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., 
      Tokyo, Japan.
FAU - Kakuyama, Hiroyoshi
AU  - Kakuyama H
AD  - Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., 
      Ltd., Tokyo, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20200930
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 0 (Morpholines)
RN  - 0 (Piperidines)
RN  - 0 (Serotonin 5-HT4 Receptor Agonists)
RN  - I7V9UD0ND0 (minesapride)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Animals
MH  - Biotransformation
MH  - Dogs
MH  - Drug Partial Agonism
MH  - Female
MH  - Healthy Volunteers
MH  - Hepatocytes/*metabolism
MH  - Humans
MH  - Japan
MH  - Macaca fascicularis
MH  - Male
MH  - Mice
MH  - Models, Biological
MH  - Morpholines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Patient Safety
MH  - Piperidines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Rabbits
MH  - Rats, Sprague-Dawley
MH  - Risk Assessment
MH  - Serotonin 5-HT4 Receptor Agonists/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - 5-HT(4) receptor agonist
OT  - Dose adjustment
OT  - Elderly
OT  - Metabolite
OT  - Minesapride
COIS- Declaration of competing interest Both studies (clinical study and in vitro 
      study) were founded by Sumitomo Dainippon Pharma Co., Ltd. T. Hamatani, Y. 
      Shibue, N. Sawada, T. Takagaki, M. Hashimoto, Y. Nakada and H. Kakuyama are 
      employees of Sumitomo Dainippon Pharma Co., Ltd.
EDAT- 2020/11/16 06:00
MHDA- 2021/08/25 06:00
CRDT- 2020/11/15 20:23
PHST- 2020/03/24 00:00 [received]
PHST- 2020/08/13 00:00 [revised]
PHST- 2020/09/25 00:00 [accepted]
PHST- 2020/11/16 06:00 [pubmed]
PHST- 2021/08/25 06:00 [medline]
PHST- 2020/11/15 20:23 [entrez]
AID - S1347-4367(20)30418-3 [pii]
AID - 10.1016/j.dmpk.2020.09.005 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2020 Dec;35(6):563-570. doi: 
      10.1016/j.dmpk.2020.09.005. Epub 2020 Sep 30.