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

Background and purpose: C-13-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 C-13-urea from colon-targeted capsules would lead to fermentation of C-13-urea by bacterial ureases into (CO2)-C-13. Subsequent absorption into the blood and circulation would lead to detectable C-13 (as (CO2)-C-13) in breath. If, however, release of C-13-urea occurred in the small intestine (urease-poor segment), we expected detectable C-13 (as C-13-urea) in blood but no breath C-13 (as (CO2)-C-13). The differential kinetics of C-13-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 C-13-in breath CO2 (F-fermented) and the appearance of C-13 in blood as C-13-urea (F-not fermented) show a high inverse correlation (Pearson's r = -0.981, P = 0.06). The total recovery of C-13 (F-fermented + F-not fermented) averaged 99%, indicating complete recovery of the administered C-13 via breath and blood. (CO2)-C-13 exhalation was observed in all subjects. This indicates that C-13-urea was available in urease-rich segments, such as the caecum or colon. Conclusions and implications: In this proof-of-concept study, C-13-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.