PMID- 35339635
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20240407
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 619
DP  - 2022 May 10
TI  - The effect of esomeprazole on the upper GI tract release and systemic absorption 
      of mesalazine from colon targeted formulations.
PG  - 121701
LID - S0378-5173(22)00256-3 [pii]
LID - 10.1016/j.ijpharm.2022.121701 [doi]
AB  - The aim of the present study was to investigate the effect of coadministration of 
      the proton pump inhibitor (PPI) esomeprazole on the upper GI tract behavior and 
      systemic exposure of mesalazine from two mechanistically different colon targeted 
      delivery systems: Claversal (pH-dependent release) and Pentasa (prolonged 
      release). To this end, gastric, jejunal and systemic concentrations of mesalazine 
      and its metabolite N-acetyl mesalazine were monitored in 5 healthy volunteers 
      following oral intake of Pentasa or Claversal with or without PPI pre-treatment 
      (cross-over study). Our exploratory study demonstrated that pre-treatment with a 
      PPI may affect the release and absorption of mesalazine from formulations with 
      different modified release mechanisms. Upon intake of Claversal, the onset of 
      mesalazine absorption was accelerated substantially by PPI pre-treatment. While 
      the PPI-induced increase in pH initiated the disintegration process already in 
      the upper GI tract, the release of mesalazine started beyond the proximal 
      jejunum. Upon intake of Pentasa, PPI pre-treatment seemed to increase the 
      systemic exposure, even though the underlying mechanism could not be revealed 
      yet. The faster release of mesalazine in the GI tract and/or the increased 
      systemic absorption following PPI pre-treatment may reduce the ability of 
      mesalazine to reach the colon. Future research assessing mesalazine disposition 
      in the lower GI tract is warranted.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Van Camp, Arno
AU  - Van Camp A
AD  - Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - 
      box 921, 3000 Leuven, Belgium. Electronic address: arno.vancamp@kuleuven.be.
FAU - Vanuytsel, Tim
AU  - Vanuytsel T
AD  - Translational Research Center for Gastrointestinal Disorders, TARGID, KU Leuven, 
      Herestraat 49, 3000 Leuven, Belgium. Electronic address: 
      tim.vanuytsel@kuleuven.be.
FAU - Brouwers, Joachim
AU  - Brouwers J
AD  - Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - 
      box 921, 3000 Leuven, Belgium. Electronic address: joachim.brouwers@kuleuven.be.
FAU - Augustijns, Patrick
AU  - Augustijns P
AD  - Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - 
      box 921, 3000 Leuven, Belgium. Electronic address: 
      patrick.augustijns@kuleuven.be.
LA  - eng
PT  - Journal Article
DEP - 20220323
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 4Q81I59GXC (Mesalamine)
RN  - N3PA6559FT (Esomeprazole)
SB  - IM
EIN - Int J Pharm. 2024 Apr 25;655:124087. PMID: 38584003
MH  - Absorption, Physiological
MH  - Colon
MH  - Cross-Over Studies
MH  - Esomeprazole/pharmacology
MH  - Humans
MH  - *Mesalamine
MH  - *Upper Gastrointestinal Tract
OTO - NOTNLM
OT  - Clinical trial
OT  - Colon targeted drug delivery systems
OT  - Drug absorption
OT  - Gastrointestinal release
OT  - Mesalazine
OT  - PPI effect
EDAT- 2022/03/28 06:00
MHDA- 2022/04/29 06:00
CRDT- 2022/03/27 20:20
PHST- 2021/12/29 00:00 [received]
PHST- 2022/03/19 00:00 [revised]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/03/28 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2022/03/27 20:20 [entrez]
AID - S0378-5173(22)00256-3 [pii]
AID - 10.1016/j.ijpharm.2022.121701 [doi]
PST - ppublish
SO  - Int J Pharm. 2022 May 10;619:121701. doi: 10.1016/j.ijpharm.2022.121701. Epub 
      2022 Mar 23.