Degradation kinetics of metronidazole and olsalazine by bacteria in ascending colon and in feces of healthy adults

作者：Vertzoni Maria^*; Carlsson Anders; Abrahamsson Berth L; Goumas Konstantinos; Reppas Christos

来源：International Journal of Pharmaceutics, 2011, 413(1-2): 81-86.

DOI：10.1016/j.ijpharm.2011.04.028

• Degradation kinetics
• Ascending colon
• Feces
• Metronidazole
• Olsalazine

Purpose:To compare the degradation kinetics of metronidazole and olsalazine by the bacteria of ascending colon and the bacteria of feces of healthy adults.
Methods: Contents of the ascending colon of seven healthy adults were collected under conditions simulating the bioavailability/bioequivalence studies in the fasted and in the fed states on a crossover basis. Material from the contents of the ascending colon was prepared by ultracentrifuging and diluting the precipitate with a volume of normal saline equivalent to that of the supernatant. Fecal material was prepared from feces of three healthy adults collected at two occasions that were separated by at least 6 months. Ex vivo drug degradation kinetics were evaluated under anaerobic conditions.
Results: Mean half-lives of metronidazole degradation in material from the contents of the ascending colon collected in the fasted state and in fecal material were 16.1 and 2.4 min, respectively (p < 0.001). The corresponding numbers for olsalazine were 57.8 and 9.2 min, respectively (p < 0.001). Both compounds were stable in material from the contents of ascending colon collected in the fed state.
Conclusions: Compared with data in fecal material, degradation of metronidazole and olsalazine in material from the contents of the ascending colon is significantly slower and it becomes non-significant during the arrival of fresh food remnants in the region.

• 出版日期2011-7-15