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

Scand J Gastroenterol. 2009;44(9):1067-75. doi: 10.1080/00365520903114904.

Abstract

Objective: To investigate the possible use of a (13)C-uracil breath test for gastric emptying by evaluating the pharmacokinetic properties of (13)C-uracil in a breath test in rats, in comparison with (13)C-acetate and (13)C-octanoate, traditional (13)C-probes for gastric emptying.

Material and methods: Absorption of the (13)C-probes from different parts of the gastrointestinal tract was evaluated in fasted rats. (13)C-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 (13)C-uracil in the stomach and correlated the amount with the breath response.

Results: All the (13)C-probes employed were well absorbed from the intestine after intraduodenal administration. After intragastric administration, (13)C-uracil was not absorbed from the stomach, but (13)C-acetate and (13)C-octanoate were partly absorbed from the stomach. The cumulative (14)C-uracil recovery (%) at 168 h was 92.3, 6.3, or 0.5%, from expired gases, urine, and feces, respectively. Delta(13)C values in (13)C-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 (13)C-uracil in the stomach after oral administration of (13)C-uracil, indicating that (13)C-uracil can be used as an in vivo probe for evaluating gastric emptying in a quantitative manner.

Conclusions: This study showed that (13)C-uracil has desirable pharmacokinetic properties as an in vivo probe of gastric emptying. It is thus suggested that the (13)C-uracil breath test may be useful for the measurement of gastric emptying in humans.

Publication types

  • Comparative Study

MeSH terms

  • Acetates / administration & dosage
  • Acetates / pharmacokinetics*
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Breath Tests / methods*
  • Caprylates / administration & dosage
  • Caprylates / pharmacokinetics*
  • Carbon Isotopes / administration & dosage
  • Carbon Isotopes / pharmacokinetics*
  • Fasting
  • Gastric Emptying / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Uracil / administration & dosage
  • Uracil / pharmacokinetics*

Substances

  • Acetates
  • Caprylates
  • Carbon Isotopes
  • Uracil
  • octanoic acid