Usefulness of breath test for evaluating pancreatic exocrine function using N-benzoyl-L-tyrosyl-1-13C-L-alanine sodium in non-invasive and conscious rats

Abstract

N-Benzoyl-L-tyrosyl-1-13C-L-alanine sodium is a dipeptide used for evaluating pancreatic exocrine function. The method of evaluation, however, is not yet satisfactory, especially in experimental animals. The relation between diabetes and pancreatic exocrine function also is not clear. Therefore, this study sought to establish a method for evaluating pancreatic exocrine function and to validate the method by determining non-invasively the effect of alloxan-induced diabetes in conscious rats. After fasting, rats were orally administered Racol containing N-benzoyl-L-tyrosyl-1-13C-L-alanine sodium or 1-13C-L-alanine and housed in desiccators. The expired air in the desiccator was collected in a breath-sampling bag using a tube and aspiration pump, and the level of 13CO2 in this air was measured using an infrared spectrometer at appropriate intervals over a 120 min period. The rate of 13CO2 excretion increased, peaked and then decreased in a dose-dependent manner. The maximum concentration and area under the curve of 13CO2 excretion significantly and positively correlated with the doses of N-benzoyl-L-tyrosyl-1- 13C-L-alanine sodium. In the rats made diabetes by the administration of alloxan, the level of expired 13CO2 air changed at significantly lower levels as compared with that of the control rats on day 3, although the level of expired 13CO2 air from 1- 13C-L-alanine was also markedly lower than that of the control rats. These results showed that pancreatic exocrine function can be evaluated using this breath test system and that alloxan-induced diabetes affects this function. © 2008 Pharmaceutical Society of Japan.