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.
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.


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.
Sugiyama
Erika
E
Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, Faculty of Pharmaceutical Sciences, Showa University, Tokyo, Japan. e-sugiyama@pharm.showa-u.ac.jp
Inada
Makoto
M
Kunizaki
Jun-Ichi
J
Tobita
Kazuki
K
Yoshida
Takahito
T
Kashimoto
Minoru
M
Hirao
Yukihiro
Y
Sato
Hitoshi
H
D000085:Acetates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001944:Breath Tests / Q000379:methods*; D002210:Caprylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005215:Fasting; D005746:Gastric Emptying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014498:Uracil / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000085:Acetates; D002210:Caprylates; D002247:Carbon Isotopes; D014498:Uracil; C031492:octanoic acid