, 1991). In earlier days, the transit of a dosage form through the GIT was visualized by using X-ray radiography with barium sulphate as a selleck compound contrast substance (Lark-Horovitz, 1941; Efimova and Minina, 1969). Today, ��-scintigraphy as a molecular imaging technology is considered to be the state-of-the art imaging technology (Digenis et al., 2000; Wilding et al., 2001; Damle et al., 2002; Willmann et al., 2008). While recognizing the advantages of the above-mentioned methods, they both carry the disadvantage of exposing subjects to ionizing radiation. Sulfasalazine has also been used to qualitatively measure the small intestinal transit time (Sunesen et al., 2005). However, sulfasalazine is not a reliable marker for showing the fraction of the dose delivered in the colon because of its limited absorption from the small intestine and its enterohepatic circulation.
Assessment of in vivo behaviour of oral drug products by pharmacokinetic assessment in combination with non-radioactive stable isotope technology is seldom performed, despite its interesting possibilities (Verbeke et al., 2005). A marker substance for colon delivery assessment should ideally fulfil several requirements. First, the marker should be able to show whether release and/or uptake takes place in the colon or in other intestinal segments. Second, the marker or its relevant metabolite should have favourable kinetics such as fast and complete absorption, short distribution time and single compartment kinetics (small volume of distribution). Only in this case will the marker kinetics reflect the release kinetics of the dosage form.
Furthermore, the safety of the marker, ease of sampling and reliable analysis are important issues. In view of these specifications, 13C-urea provides an interesting possibility. We proposed that release of 13C-urea in the caecum or colon (urease-rich segment) from oral colon-targeted capsules would lead to fermentation of 13C-urea by bacterial urease into 13CO2 (Lee et al., 2003; Urita et al., 2006). Subsequent absorption of 13CO2 into the blood and circulation would lead to detectable 13C (as 13CO2) in breath. If, however, release of 13C-urea already occurs in the small intestine (urease-poor segment), only detectable 13C (as 13C-urea) in the blood is expected, as the bioavailability of 13C-urea is near 100%. Consequently, no 13C (as 13CO2) in breath will be detectable in the latter situation.
This differential kinetics of 13C-urea (Figure 1) could potentially describe both the kinetics of release and serve as an indicator for the GI segment of release. Figure 1 Absorption, metabolism and AV-951 elimination of 13C-urea upon release in the small intestine versus release in the caecum or colon. The weight of the line symbolizes the relative importance of the corresponding kinetic process. 13C-urea delivered in the small …