First, the kinetic profile of coated dosage forms Bosutinib may be monitored based on only breath samples. The lag time and Ffermented (and its corresponding Fnot fermented) can be obtained. In our experimental setup, a subsequent meal was used in order to standardize and control the intestinal transit of the capsule. As this standardized subsequent meal is not present in clinical practice, it should preferably be omitted when carrying out a bioavailability study. Second, any statement on the availability in any GI segment depends on the biological dogma that fermentation does not occur in the small intestine as it is a urease-poor segment. A wealth of information is available on fermentation processes in the GIT (Cummings et al., 2001; Wong and Jenkins, 2007), and all studies conclude that under physiological situations (i.

e. no bacterial overgrowth), no relevant fermentation occurs in the small intestine. Furthermore, urease is not produced by humans but only by bacteria, yeasts and several higher plants. Therefore, 13C-urea is considered a safe marker substance, able to provide information on the GI segment of release in humans. In conclusion, we performed the first proof-of-concept study on the application of 13C-urea as a marker substance for effective colon delivery. It was shown that 13C-urea is able to provide information on both the release kinetics of a colon-targeted oral dosage form and the GI segment of release. 13C-urea fulfils both roles based on the combination of suitable physico-chemical and kinetic characteristics as well as an excellent safety profile.

Further validation studies in healthy volunteers and patients should evaluate its potential in assessing the performance of colon delivery dosage forms and the impact of inter-individual and intra-individual variance in 13C-urea absorption and fermentation on these assessments. Evaluation of colon-targeted oral dosage forms may be performed by analysing the 13C-appearance in breath only. This opens new possibilities in performing biopharmaceutical studies to improve the therapy of diseases occurring locally in the colon or in which drugs are used that require colonic delivery. Acknowledgments We thank Dr V Fidler for his valuable comments on the statistical calculations. Glossary Abbreviations: GIT gastrointestinal tract H. pylori Helicobacter pylori LNA Laboratory of Dutch Pharmacists OCTT oro-caecal transit time Ph.

Eur. European Pharmacopoeia UDV urea distribution volume WFI water for injections Conflict Cilengitide of interest None.
Males and females are sexually dimorphic because of divergent selection in many traits, including morphology, physiology, life history, and behavior. In fact, the most extreme differences described within species, such as body size, are often those between sexes and, typically, sex differences explain most of the phenotypic variation between adults in a sexual population.