| Autor: |
Schellekens, RCA, Olsder, GG, Langenberg, SMCH, Boer, T, Woerdenbag, HJ, Frijlink, HW, Kosterink, JGW, Stellaard, F, Schellekens, R C A, Olsder, G G, Langenberg, S M C H, Woerdenbag, H J, Frijlink, H W, Kosterink, J G W |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Sep2009, Vol. 158 Issue 2, p532-540, 9p |
| Abstrakt: |
Background and Purpose: (13)C-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 (13)C-urea from colon-targeted capsules would lead to fermentation of (13)C-urea by bacterial ureases into (13)CO(2). Subsequent absorption into the blood and circulation would lead to detectable (13)C (as (13)CO(2)) in breath. If, however, release of (13)C-urea occurred in the small intestine (urease-poor segment), we expected detectable (13)C (as (13)C-urea) in blood but no breath (13)C (as (13)CO(2)). The differential kinetics of (13)C-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 (13)C-in breath CO(2) (F(fermented)) and the appearance of (13)C in blood as (13)C-urea (F(not fermented)) show a high inverse correlation (Pearson's r=-0.981, P= 0.06). The total recovery of (13)C (F(fermented)+F(not fermented)) averaged 99%, indicating complete recovery of the administered (13)C via breath and blood. (13)CO(2) exhalation was observed in all subjects. This indicates that (13)C-urea was available in urease-rich segments, such as the caecum or colon.Conclusions and Implications: In this proof-of-concept study, (13)C-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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