Prague Med. Rep. 2019, 120, 5-9

https://doi.org/10.14712/23362936.2019.5

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

Martin Šíma, Nikolina Kutinová-Canová, Pavel Ryšánek, Jana Hořínková, Denisa Moškořová, Ondřej Slanař

Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

Received November 14, 2018
Accepted May 2, 2019

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.

Funding

This study was supported by the Charles University Project Progres Q25 and a grant no. SVV 260373.

References

8 live references