Calcium [¹³C]carbonate breath test for quantitative measurement of total gastric acid in rats.
OBJECTIVE
A traditional measurement of gastric acid, involving nasogastric intubation of stomach and acid suction, has been suggested as a gold standard. However, this causes the patient discomfort and cost increase, and is 'time-consuming'.


METHODS
A calcium [(13)C]carbonate (Ca(13)CO(3)) breath test was carried out in rats without or with concomitant drugs omeprazole (OMP) and pentagastrin (PG) known as an inhibitor and an inducer of acid, respectively. This test was aimed at evaluating a correlation between the breath response and the total amount of gastric acid. To search for an absorption pathway of (13)CO(2) gas produced by the reaction of Ca(13)CO(3) with hydrochloric acid in the stomach of rats, we compared the breath responses after intra-gastric administration of (13)CO(2) gas and sodium [(13)C]bicarbonate (NaH(13)CO(3)).


RESULTS
A linear relationship of the breath parameter (breath-C(max)) with the dose of Ca(13)CO(3) was obtained in the range of 4-200 µmol/kg. However, theses parameters were saturated at >200 µmol/kg. The direct correlation between the breath-C(max) and the total amount of gastric acid in rats with or without OMPs or PG (r = 0.994) demonstrated that the change in breath response is an accurate or sensitive indicator of the total amount of gastric acid. (13)CO(2) gas generated in the rat stomach was likely to diffuse across the stomach wall as (13)CO(2) gas directly into the blood plasma.


CONCLUSIONS
The present study showed that Ca(13)CO(3) breath test is a good tool to accurately predict the total amount of gastric acid.
Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, Diagnostic Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan. inadam@otsuka.jp
Makoto
M
Inada
Jun-ichi
J
Kunizaki
Kazuki
K
Tobita
Suguru
S
Akamatsu
Hitoshi
H
Sato
D000818:Animals; D001944:Breath Tests; D002119:Calcium Carbonate / Q000032:analysis*; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000378:metabolism; D002247:Carbon Isotopes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017693:Sodium Bicarbonate / Q000008:administration & dosage
D002247:Carbon Isotopes; D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D017693:Sodium Bicarbonate; D010418:Pentagastrin; D002119:Calcium Carbonate; D009853:Omeprazole