Modification of gastric pH in the fasted dog.
OBJECTIVE
The aim was to compare the ability of pretreatments to consistently adjust gastric conditions to low or high pH in the fasted state in dogs.


METHODS
Four male Labrador/Labrador-cross dogs weighing 25-35 kg were surgically equipped with a ventricle fistula cannula in the stomach and a jejunal nipple valve stoma. Dogs were fasted overnight before the experiments, with free access to water. The pH in the dogs' stomach was modified either orally with buffers (0.1 mol/l HCl-KCl, 0.05 mol/l glycine-HCl, 0.1 mol/l citrate or 0.1 mol/l BIS-TRIS) or intravenously with pharmacological agents (pentagastrin 4-6 microg/kg, ranitidine 50 mg or omeprazole 1 mg/kg). Intragastric pH was recorded continuously for 2 h with an electrode connected to an ambulatory pH meter. Chyme was collected simultaneously from the jejunal stoma as an approximate measure of gastric emptying.


RESULTS
0.1 mol/l HCl-KCl buffer p.o. and 1 mg/kg omeprazole i.v. attained low and high gastric pH more reproducibly (11/11 and 6/7 experiments met target values of pH < 3 and > 4, respectively) and for a longer duration (average time exceeding target value 90 and 103 min, respectively) than the other buffers and pharmacological pretreatments. The starting pH did not alter the modifiers' capacity to increase or decrease the pH. However, the lag time before chyme appeared at the jejunal stoma appeared to be longer when the pH was low and shorter when the pH was high.


CONCLUSIONS
To achieve a consistently low gastric pH in fasting dogs, 0.1 mol/l HCl-KCl buffer should be administered orally, 15 min before the dosage form. To elevate the gastric pH reproducibly, omeprazole 1 mg/kg should be administered intravenously at least 90 min before oral administration of the dosage form.
Polentarutti
Britta
B
Early Development, Pharmaceutical and Analytical R&D, AstraZeneca R&D Mölndal, Sweden.
Albery
Tamsin
T
Dressman
Jennifer
J
Abrahamsson
Bertil
B
D000818:Animals; D002021:Buffers; D004285:Dogs; D005215:Fasting; D005746:Gastric Emptying; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D007275:Injections, Intravenous; D007583:Jejunum; D008297:Male; D023421:Models, Animal; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology; D013270:Stomach / Q000737:chemistry / Q000187:drug effects*; D013997:Time Factors
D002021:Buffers; D011189:Potassium Chloride; D011899:Ranitidine; D010418:Pentagastrin; D009853:Omeprazole; D006851:Hydrochloric Acid; D005998:Glycine