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Sarit Cohen Rabbie1, Talia Flanagan2, Paul D Martin2

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Drug solubility in ileostomy fluids varies significantly, impacting oral drug absorption. This variability in buffer capacity and pH helps explain inconsistent drug bioavailability in patients with ulcerative colitis.

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Drug Delivery

Background:

  • Oral drug absorption variability is a known issue in drug delivery.
  • Understanding absorption variability is key for predicting drug pharmacokinetics.
  • Furosemide and dipyridamole exhibit highly variable oral bioavailabilities.

Purpose of the Study:

  • To investigate the solubility of furosemide and dipyridamole in individual ileostomy fluids.
  • To compare drug solubility in ileostomy fluids with pooled gastrointestinal fluids and simulated fluids.
  • To elucidate the factors contributing to drug solubility variability in ileostomy fluids.

Main Methods:

  • Collected individual ileostomy fluids from 10 ulcerative colitis subjects.
  • Determined drug solubility of furosemide and dipyridamole in ileostomy fluids.
  • Characterized ileostomy fluid properties, including pH and buffer capacity.
  • Compared solubility in ileostomy fluids with pooled upper GI fluids and simulated intestinal fluids.

Main Results:

  • Ileostomy fluids exhibited significant variability in buffer capacity and pH.
  • Furosemide and dipyridamole solubility showed high variability in ileostomy fluids.
  • Dipyridamole solubility correlated with pH; furosemide solubility correlated with both buffer capacity and pH.

Conclusions:

  • Ileostomy fluid properties (pH, buffer capacity) significantly influence drug solubility.
  • Variability in drug solubility within the gastrointestinal tract may partly explain inconsistent oral bioavailability.
  • These findings highlight the importance of considering individual patient fluid characteristics in oral drug delivery.