Desirable pharmacokinetic properties of ¹³C-uracil as a breath test probe of gastric emptying in comparison with ¹³C-acetate and ¹³C-octanoate in rats

Abstract

Objective. To investigate the possible use of a ¹³C-uracil breath test for gastric emptying by evaluating the pharmacokinetic properties of ¹³C-uracil in a breath test in rats, in comparison with ¹³C-acetate and ¹³C-octanoate, traditional ¹³C-probes for gastric emptying. Material and methods. Absorption of the ¹³C-probes from different parts of the gastrointestinal tract was evaluated in fasted rats. ¹³C-Uracil breath tests for gastric emptying were carried out in conditions where delayed gastric emptying was induced by clonidine, quinpirole, and propantheline, and in a postoperative ileus model. Following oral administration, we measured residual ¹³C-uracil in the stomach and correlated the amount with the breath response. Results. All the ¹³C-probes employed were well absorbed from the intestine after intraduodenal administration. After intragastric administration, ¹³C-uracil was not absorbed from the stomach, but ¹³C-acetate and ¹³C-octanoate were partly absorbed from the stomach. The cumulative ¹⁴C-uracil recovery (%) at 168 h was 92.3, 6.3, or 0.5%, from expired gases, urine, and feces, respectively. Δ¹³C values in ¹³C-uracil breath tests were decreased in conditions characterized by delayed gastric emptying. A highly negative correlation was observed between the breath response and the residual ratio of ¹³C-uracil in the stomach after oral administration of ¹³C-uracil, indicating that ¹³C-uracil can be used as an in vivo probe for evaluating gastric emptying in a quantitative manner. Conclusions. This study showed that ¹³C-uracil has desirable pharmacokinetic properties as an in vivo probe of gastric emptying. It is thus suggested that the ¹³C-uracil breath test may be useful for the measurement of gastric emptying in humans.

• Absorption
• breath test
• ¹³C-acetate
• ¹³C-octanoate
• ¹³C-uracil
• gastric emptying