Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms

Abstract

Background and purpose: 13C-urea may be a suitable marker to assess the in vivo fate of colon-targeted dosage forms given by mouth. We postulated that release in the colon (urease-rich segment) of 13C-urea from colon-targeted capsules would lead to fermentation of 13C-urea by bacterial ureases into 13CO 2. Subsequent absorption into the blood and circulation would lead to detectable 13C (as 13CO 2) in breath. If, however, release of 13C-urea occurred in the small intestine (urease-poor segment), we expected detectable 13C (as 13C-urea) in blood but no breath 13C (as 13CO 2). The differential kinetics of 13C-urea could thus potentially describe both release kinetics and indicate the gastrointestinal segment of release. Experimental approach: The in vivo study consisted of three experiments, during which the same group of four volunteers participated. Key results: The kinetic model was internally valid. The appearance of 13C-in breath CO 2 (F fermented) and the appearance of 13C in blood as 13C-urea (F not fermented) show a high inverse correlation (Pearson's r = -0.981, P = 0.06). The total recovery of 13C (F fermented + F not fermented) averaged 99%, indicating complete recovery of the administered 13C via breath and blood. 13CO 2 exhalation was observed in all subjects. This indicates that 13C-urea was available in urease-rich segments, such as the caecum or colon. Conclusions and implications: In this proof-of-concept study, 13C-urea was able to provide information on both the release kinetics of a colon-targeted oral dosage form and the gastrointestinal segment where it was released. © 2009 The British Pharmacological Society.