Τίτλος:
Ex vivo evaluation of degradation rates of metronidazole and olsalazine in distal ileum and in cecum: The impact of prandial state
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose Evaluate ex vivo the bacterial metabolism induced degradation rates of mesalamine (negative control), metronidazole and olsalazine in distal ileum and in cecum. Methods The contents of distal ileum and cecum were collected during colonoscopy under anaerobic conditions from twelve healthy adults in the fasted and in the fed state. To eliminate potential effects of enzymes that may exist in the fluid of lower intestine, each sample was ultracentrifuged and the precipitate was diluted with a volume of normal saline equivalent to that of the supernatant, after ultracentrifugation of intestinal contents from which the specific precipitate had been obtained. Degradation of the three model drugs in individual materials was evaluated anaerobically. Results Mesalamine was stable in all cases. Degradation rates of metronidazole and olsalazine were higher in cecum than in distal ileum, only in the fasted state; no trend could be observed in the fed state. Degradation rates of metronidazole and olsalazine were decreased in the fed state in the cecum; no trend could be observed in distal ileum. Conclusions In the fasted state, bacterial activity is higher in cecum than in distal ileum. Food residues decrease bacterial metabolism degradation rates of drugs in cecum. © 2017 Elsevier B.V.
Συγγραφείς:
Karatza, E.
Goumas, C.
Muenster, U.
Reppas, C.
Vertzoni, M.
Περιοδικό:
International Journal of Pharmaceutics
Λέξεις-κλειδιά:
azo reductase; mesalazine; metronidazole; nitroreductase; olsalazine; aminosalicylic acid derivative; mesalazine; metronidazole; olsalazine, Article; ascending colon; bacterial metabolism; cecum; colonoscopy; competitive inhibition; controlled study; degradation kinetics; diet restriction; drug degradation; drug half life; enzyme activity; ex vivo study; human; human experiment; ileum; microbial activity; nonhuman; normal human; priority journal; adult; bacterium; metabolism, Adult; Aminosalicylic Acids; Bacteria; Cecum; Fasting; Humans; Ileum; Mesalamine; Metronidazole
DOI:
10.1016/j.ijpharm.2017.10.015
