Stability of ketoprofen-dextran ester prodrugs in homogenates of various segments of pig GI tract

Publication: Research - peer-reviewJournal article – Annual report year: 1991

Without internal affiliation

  • Author: Larsen, C.

    Royal Danish School of Pharmacy, Denmark

  • Author: Jensen, Bodil Hamborg

    University of Copenhagen

  • Author: Olesen, H. P.

    Royal Danish School of Pharmacy, Denmark

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Initial velocities of ketoprofen formation from ketoprofen-dextran ester prodrugs incubated in homogenates of various segments of the pig GI-tract were determined. Enzyme-mediated drug release was found in caecum and colon homogenates with their contents, whereas release rates in the stomach, duodenum, jejunum and ileum homogenates were comparable to those determined in pure buffer solutions of identical pH. In colon homogenates adjusted to various pH values between 6.0 and 7.9, little variation in release rates was observed. However, the contribution of enzyme-catalyzed drug regeneration to the overall initial velocity of ketoprofen formation increased significantly as a function of decreasing pH. The presence of several antibiotics and betamethasone in colon homogenates did not affect the drug activation process, whereas the addition of various enzyme inhibitors slowed down the ketoprofen release rates. During incubation in colon homogenates the average molecular weight of the dextran esters decreased. The drug release may therefore involve an initial fragmentation of the drug-liganded dextran chains carried out by dextranases secreted from the microflora which reside in the pig's large bowel.
Original languageEnglish
JournalActa Pharmaceutica Nordica
Issue number1
Pages (from-to)41-44
StatePublished - 1991
Externally publishedYes
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ID: 3293014