Inclusion complexation of warfarin withβ-cyclodextrins and its influence on absorption kinetics of warfarin in rat

  • O. Karadaĝ
  • E. Gök
  • I. Serdar Ates
  • Ö. Kiran
  • A. Bozkurt
Article

Abstract

The inclusion complexes of warfarin withβ-cyclodextrin, 2-hydroxypropyl-β-CD and methyl-β-CD have been investigated in aqueous solution. The apparent binding constants of warfarin are found to be 542±19, 442±18 and 112±6M−1 respectively, calculated from the increments in fluorescence emission of the drug. The influence of theβ-CDs on the absorption rate of the drug is investigated within situ experiments in a chronically isolated internal loop, in the small intestine of the rat. The first-order disappearance (absorption) rate constant decreases to 3.6×10−4 min−1 inβ-CD, to 5.0×10−4 min−1 in 2-hydroxypropyl-β-CD and to 1.4×10−3 min−1 in methyl-β-CD compared to 3.2×10−3 min−1 in isotonic phosphate buffer (pH=7.4) solution, all of them showing a good agreement with the percentage of free warfarin in their complexed solutions: 16%, 18% and 47% calculated, respectively.

Key words

Inclusion complexation of warfarin withβ-CDs apparent binding constants bioavailability of warfarin β-CD complexes fluorescence spectroscopy β-cyclodextrin 2-hydroxypropyl-β-cyclodextrin methyl-β-cyclodextrin 

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • O. Karadaĝ
    • 1
  • E. Gök
    • 1
  • I. Serdar Ates
    • 1
  • Ö. Kiran
    • 2
  • A. Bozkurt
    • 2
  1. 1.Department of Chemistry, Faculty of ScienceHacettepe UniversityAnkaraTurkey
  2. 2.Department of Pharmacology, Faculty of MedicineHacettepe UniversityAnkara

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