A difference in dissolution profile is not a probable major selleck chemicals Olaparib explanation for the slower pulse in the urease-rich segments as shown by our 13CO2 results. Furthermore, the Ffermented (not corrected for CO2 retention) for 13C-urea in coated capsules was lower than for 13C-bicarbonate in coated capsules. This may be the result of various factors. A (small) part of the liberated urea escapes fermentation by being absorbed quickly or by being utilized as a substrate by bacteria to form other metabolites than CO2 and NH3. Urea is also being lost through the faeces in a small amount (<4%) (Billich and Levitan, 1969; Moran and Jackson, 1990). The lag times, as determined for the appearance of 13C in breath or plasma after intake of a coated capsule containing 13C-urea, showed little difference.

This points to the fact that fermentation and absorption occur simultaneously. Because urea may be absorbed both from the small intestine and from the caecum and colon (Billich and Levitan, 1969; Moran and Jackson, 1990), no concluding statements can be made with respect to the location of the absorption process of intact urea. However, when the 13C-recoveries from blood and breath after intake of a coated capsule with 13C-urea are analysed head to head and in more detail (Figures 2 and and3),3), it is observed that 13C-urea appeared in the circulation around the moment the subsequent meal is taken. Then, shortly after the appearance of 13C-urea in blood and after intake of the subsequent meal, 13C was also detected in breath.

This observation leads to the hypothesis that nearly all 13C-urea had been released in the terminal ileum and that some absorption takes place at that site. Then, the intake of the subsequent meal induced the transfer of the remaining 13C-urea into the urease-rich segments (caecum or colon). Absorption of intact 13C-urea continues, but now, bacteria start to ferment 13C-urea into 13CO2, which is subsequently absorbed as 13C-bicarbonate. No clear relationship could be observed between the lag times and the Ffermented. The lack of relationship can be understood as a consequence of the experimental setup; the lag times are controlled (i.e. maximized at 3 h) by taking the second meal (Priebe et al., 2004; 2006; Schellekens et al., 2008). Moreover, the trend line (Figure 4) depicts the inverse relation between the availabilities of fermented and not fermented urea.

It shows that when no urea is fermented, all is absorbed. In addition, when 100% of the urea is delivered in Entinostat urease-rich segments, little resorption of not fermented 13C-urea is to be expected. All four cases fit well into the model, as is concluded from the Pearson’s r values. This opens the possibility to evaluate colon delivery dosage forms by collecting breath samples only. Urine samples instead of blood samples may be used to verify that all urea is released.