TY - JOUR
TI - Degradation kinetics of metronidazole and olsalazine by bacteria in ascending colon and in feces of healthy adults
AU - Vertzoni, M.
AU - Carlsson, A.
AU - Abrahamsson, B.
AU - Goumas, K.
AU - Reppas, C.
JO - International Journal of Pharmaceutics
PY - 2011
VL - 413
TODO - 1-2
SP - 81-86
PB - 
SN - 0378-5173
TODO - 10.1016/j.ijpharm.2011.04.028
TODO - metronidazole;  olsalazine;  sodium chloride, adult;  anaerobic digestion;  article;  ascending colon;  controlled study;  degradation kinetics;  diet restriction;  drug bioavailability;  ex vivo study;  feces analysis;  human;  human experiment;  material state;  normal human;  precipitation;  priority journal;  ultracentrifugation, Adult;  Aminosalicylic Acids;  Anti-Infective Agents;  Bacteria;  Colon, Ascending;  Feces;  Female;  Gastrointestinal Agents;  Humans;  Male;  Metronidazole;  Middle Aged;  Young Adult
TODO - 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. © 2011 Elsevier B.V. All Rights Reserved.
ER -