PMID- 38367298
OWN - NLM
STAT- MEDLINE
DCOM- 20240422
LR  - 20240422
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 55
DP  - 2024 Apr
TI  - Preferential meropenem absorption activated by 1alpha,25-dihydroxyvitamin D(3) and 
      shared with foscarnet, a phosphate transporter substrate, in the rat ileum.
PG  - 100997
LID - S1347-4367(24)00003-X [pii]
LID - 10.1016/j.dmpk.2024.100997 [doi]
AB  - Meropenem (MEPM) is used for the treatment of serious infectious diseases solely 
      as. INJECTABLE: Therefore, the development of an oral formulation would expand 
      its clinical utility. To this end, an exact understanding of the absorption 
      characteristics of MEPM is essential. In this study, MEPM absorption in the rat 
      small intestine was investigated using an in situ loop technique and an in vitro 
      diffusion chamber method. The disappearance ratios of MEPM (0.1 mM) were in the 
      order of ileum > duodenum > jejunum. The extensive MEPM disappearance in the 
      ileum was significantly reduced in the presence of foscarnet, a Na(+)-dependent 
      phosphate transporter (NaPi-T) substrate, whereas glycylsarcosine, thiamine, 
      taurocholic acid, and biapenem had no effects. The mucosal-to-serosal (M-to-S) 
      permeation of MEPM across the rat ileal segments was very small under normal 
      experimental conditions. However, on addition of 1alpha,25-dihydroxyvitamin D(3) 
      (1,25(OH)(2)D(3)) to the experimental medium, the M-to-S permeation of MEPM 
      markedly increased, showing a more than 7-fold greater apparent permeation 
      coefficient. The present results suggest that MEPM is preferentially absorbed in 
      the rat ileum, sharing with foscarnet, and that 1,25(OH)(2)D(3) potentially 
      activates the absorption of MEPM there. A likely candidate for involvement in 
      MEPM absorption was NaPi-T or a related transporter.
CI  - (c) 2024 Published by Elsevier Ltd on behalf of The Japanese Society for the Study 
      of Xenobiotics.
FAU - Saito, Toshihide
AU  - Saito T
AD  - Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences 
      University of Hokkaido, Ishikari, Tobetsu, Hokkaido, 061-0293, Japan.
FAU - Ichimura, Yuichi
AU  - Ichimura Y
AD  - Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences 
      University of Hokkaido, Ishikari, Tobetsu, Hokkaido, 061-0293, Japan.
FAU - Oda, Masako
AU  - Oda M
AD  - Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences 
      University of Hokkaido, Ishikari, Tobetsu, Hokkaido, 061-0293, Japan.
FAU - Saitoh, Hiroshi
AU  - Saitoh H
AD  - Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences 
      University of Hokkaido, Ishikari, Tobetsu, Hokkaido, 061-0293, Japan. Electronic 
      address: saitoh@hoku-iryo-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20240111
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 66772-14-3 (1,25-dihydroxyvitamin D)
RN  - 364P9RVW4X (Foscarnet)
RN  - FV9J3JU8B1 (Meropenem)
RN  - 0 (Phosphate Transport Proteins)
RN  - 1406-16-2 (Vitamin D)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Foscarnet/pharmacology
MH  - Meropenem/pharmacology
MH  - *Phosphate Transport Proteins
MH  - Ileum
MH  - Intestinal Absorption
MH  - Vitamin D/*analogs & derivatives
OTO - NOTNLM
OT  - 1alpha,25-dihydroxyvitamin D(3)
OT  - Foscarnet
OT  - In situ and in vitro discrepancy
OT  - Meropenem absorption
OT  - Rat ileum
COIS- Declaration of competing interest None.
EDAT- 2024/02/17 21:44
MHDA- 2024/04/22 06:42
CRDT- 2024/02/17 18:00
PHST- 2023/10/03 00:00 [received]
PHST- 2023/12/24 00:00 [revised]
PHST- 2024/01/09 00:00 [accepted]
PHST- 2024/04/22 06:42 [medline]
PHST- 2024/02/17 21:44 [pubmed]
PHST- 2024/02/17 18:00 [entrez]
AID - S1347-4367(24)00003-X [pii]
AID - 10.1016/j.dmpk.2024.100997 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2024 Apr;55:100997. doi: 10.1016/j.dmpk.2024.100997. 
      Epub 2024 Jan 11.