PMID- 23829508
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20181202
IS  - 1742-7843 (Electronic)
IS  - 1742-7835 (Linking)
VI  - 113
IP  - 6
DP  - 2013 Dec
TI  - Sustained Increase in the Oral Bioavailability of Loperamide after a Single Oral 
      Dose of HM30181, a P-glycoprotein Inhibitor, in Healthy Male Participants.
PG  - 419-24
LID - 10.1111/bcpt.12108 [doi]
AB  - HM30181 is a new P-glycoprotein (P-gp) inhibitor. This study was conducted to 
      investigate the effect of HM30181 and its duration of action on P-gp inhibition 
      using loperamide as a probe drug. An open-label, five-period, fixed-sequence, 
      cross-over study was conducted in 25 healthy Korean participants, who received a 
      single oral dose of loperamide at 16 mg in five periods lasting for 17 days. In 
      period II, participants also randomly received a single oral dose of HM30181 at 
      1, 5, 10, 15 mg simultaneously with loperamide. Serial pharmacokinetic blood 
      samples were obtained up to 72 and 336 hr after loperamide and HM30181 
      administration, respectively. A mixed-effects analysis was performed to compare 
      the area under the plasma concentration versus time curve from time 0 to 72 hr 
      (AUC0-72 hr ) between periods and HM30181 dose groups. Tolerability was also 
      assessed. The AUC0-72 hr of repeatedly administered loperamide was significantly 
      increased 1.18-1.62 times for up to 14 days after a single oral administration of 
      HM30181, particularly at doses >/=10 mg although the between-group difference 
      failed to reach statistical significance. Plasma HM30181 was not detected in many 
      participants including none at any sampling points beyond 48 hr after 
      administration. Most adverse events (AEs) were mild to moderate and resolved 
      spontaneously. The oral bioavailability of loperamide was significantly enhanced 
      by a single oral administration of HM30181, which was sustained for up to 
      14 days. HM30181 was well tolerated in this selected population.
CI  - (c) 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.
FAU - Cha, Yu-Jung
AU  - Cha YJ
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Lee, Howard
AU  - Lee H
AD  - Clinical Trials Center, Seoul National University Hospital, Seoul, Korea.
FAU - Gu, Namyi
AU  - Gu N
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Kim, Tae-Eun
AU  - Kim TE
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Lim, Kyoung S
AU  - Lim KS
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Yoon, Seo H
AU  - Yoon SH
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Chung, Jae-Yong
AU  - Chung JY
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Jang, In-Jin
AU  - Jang IJ
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Shin, Sang-Goo
AU  - Shin SG
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Yu, Kyung-Sang
AU  - Yu KS
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Cho, Joo-Youn
AU  - Cho JY
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine, Seoul National University Hospital, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130807
PL  - England
TA  - Basic Clin Pharmacol Toxicol
JT  - Basic & clinical pharmacology & toxicology
JID - 101208422
RN  - 0 (4-oxo-4H-chromene-2-carboxylic acid 
      (2-(2-(4-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl)-phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl)amide)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Benzopyrans)
RN  - 0 (Isoquinolines)
RN  - 0 (Tetrazoles)
RN  - 6X9OC3H4II (Loperamide)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*antagonists & inhibitors
MH  - Administration, Oral
MH  - Adult
MH  - Benzopyrans/*pharmacology
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Humans
MH  - Isoquinolines/*pharmacology
MH  - Loperamide/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Tetrazoles/*pharmacology
MH  - Young Adult
EDAT- 2013/07/09 06:00
MHDA- 2015/11/10 06:00
CRDT- 2013/07/09 06:00
PHST- 2013/05/10 00:00 [received]
PHST- 2013/06/28 00:00 [accepted]
PHST- 2013/07/09 06:00 [entrez]
PHST- 2013/07/09 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
AID - 10.1111/bcpt.12108 [doi]
PST - ppublish
SO  - Basic Clin Pharmacol Toxicol. 2013 Dec;113(6):419-24. doi: 10.1111/bcpt.12108. 
      Epub 2013 Aug 7.