Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption

Data on gastric pH in rats to be used in preclinical models for pH-dependent drug absorption are still limited or contradictory. The aim of this study was to describe gastric pH in rats at fasted state and to evaluate its changes induced by pentagastrin or omeprazole in order to mimic gastric pH at...

Full description

Bibliographic Details
Main Authors: Martin Šíma, Nikolina Kutinová-Canová, Pavel Ryšánek, Jana Hořínková, Denisa Moškořová, Ondřej Slanař
Format: Article
Language:English
Published: Karolinum Press 2019-01-01
Series:Prague Medical Report
Subjects:
Online Access:https://pmr.lf1.cuni.cz/120/1/0005/
_version_ 1818575607991107584
author Martin Šíma
Nikolina Kutinová-Canová
Pavel Ryšánek
Jana Hořínková
Denisa Moškořová
Ondřej Slanař
author_facet Martin Šíma
Nikolina Kutinová-Canová
Pavel Ryšánek
Jana Hořínková
Denisa Moškořová
Ondřej Slanař
author_sort Martin Šíma
collection DOAJ
description Data on gastric pH in rats to be used in preclinical models for pH-dependent drug absorption are still limited or contradictory. The aim of this study was to describe gastric pH in rats at fasted state and to evaluate its changes induced by pentagastrin or omeprazole in order to mimic gastric pH at fasted and fed human subjects. Twenty Wistar rats, fasting for 12 h, were randomly assigned into four treatment groups (n=5): control, pre-treated with omeprazole 2 h before pH measurement, pre-treated with omeprazole 12 h before pH measurement, and pre-treated with pentagastrin 20 min before pH measurement. An incision on the stomach wall was made in anesthetized animals, and pH of gastric juice was measured. The observed pH values were significantly different among groups (p=0.0341), with the median (IQR) values of gastric pH of 3.5 (2.7–4.2), 6.7 (4.7–7.0), 5.6 (3.5–6.4) and 2.2 (1.6–3.1) in control, omeprazole 2 h, omeprazole 12 h and pentagastin group, respectively. We recommend using short interval pentagastrin and 2 h omeprazole pre-treatment in fasting animals to model similar gastric pH as is expected in human fasted and fed state pharmacokinetic studies, respectively.
first_indexed 2024-12-15T00:43:15Z
format Article
id doaj.art-36acc845af964e239dfff7493a285d1c
institution Directory Open Access Journal
issn 1214-6994
2336-2936
language English
last_indexed 2024-12-15T00:43:15Z
publishDate 2019-01-01
publisher Karolinum Press
record_format Article
series Prague Medical Report
spelling doaj.art-36acc845af964e239dfff7493a285d1c2022-12-21T22:41:36ZengKarolinum PressPrague Medical Report1214-69942336-29362019-01-0112015910.14712/23362936.2019.5Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug AbsorptionMartin Šíma0Nikolina Kutinová-Canová1Pavel Ryšánek2Jana Hořínková3Denisa Moškořová4Ondřej Slanař5Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech RepublicInstitute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech RepublicInstitute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech RepublicInstitute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech RepublicInstitute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech RepublicInstitute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech RepublicData on gastric pH in rats to be used in preclinical models for pH-dependent drug absorption are still limited or contradictory. The aim of this study was to describe gastric pH in rats at fasted state and to evaluate its changes induced by pentagastrin or omeprazole in order to mimic gastric pH at fasted and fed human subjects. Twenty Wistar rats, fasting for 12 h, were randomly assigned into four treatment groups (n=5): control, pre-treated with omeprazole 2 h before pH measurement, pre-treated with omeprazole 12 h before pH measurement, and pre-treated with pentagastrin 20 min before pH measurement. An incision on the stomach wall was made in anesthetized animals, and pH of gastric juice was measured. The observed pH values were significantly different among groups (p=0.0341), with the median (IQR) values of gastric pH of 3.5 (2.7–4.2), 6.7 (4.7–7.0), 5.6 (3.5–6.4) and 2.2 (1.6–3.1) in control, omeprazole 2 h, omeprazole 12 h and pentagastin group, respectively. We recommend using short interval pentagastrin and 2 h omeprazole pre-treatment in fasting animals to model similar gastric pH as is expected in human fasted and fed state pharmacokinetic studies, respectively.https://pmr.lf1.cuni.cz/120/1/0005/Gastric pHRatsOral drug absorptionOmeprazolePentagastrin
spellingShingle Martin Šíma
Nikolina Kutinová-Canová
Pavel Ryšánek
Jana Hořínková
Denisa Moškořová
Ondřej Slanař
Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption
Prague Medical Report
Gastric pH
Rats
Oral drug absorption
Omeprazole
Pentagastrin
title Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption
title_full Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption
title_fullStr Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption
title_full_unstemmed Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption
title_short Gastric pH in Rats: Key Determinant for Preclinical Evaluation of pH-dependent Oral Drug Absorption
title_sort gastric ph in rats key determinant for preclinical evaluation of ph dependent oral drug absorption
topic Gastric pH
Rats
Oral drug absorption
Omeprazole
Pentagastrin
url https://pmr.lf1.cuni.cz/120/1/0005/
work_keys_str_mv AT martinsima gastricphinratskeydeterminantforpreclinicalevaluationofphdependentoraldrugabsorption
AT nikolinakutinovacanova gastricphinratskeydeterminantforpreclinicalevaluationofphdependentoraldrugabsorption
AT pavelrysanek gastricphinratskeydeterminantforpreclinicalevaluationofphdependentoraldrugabsorption
AT janahorinkova gastricphinratskeydeterminantforpreclinicalevaluationofphdependentoraldrugabsorption
AT denisamoskorova gastricphinratskeydeterminantforpreclinicalevaluationofphdependentoraldrugabsorption
AT ondrejslanar gastricphinratskeydeterminantforpreclinicalevaluationofphdependentoraldrugabsorption