Influence of Hydrodynamics and Particle Size on the Absorption of Felodipine in Labradors View Full Text


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Article Info

DATE

2002-01

AUTHORS

Annette Scholz, Bertil Abrahamsson, Steffen M. Diebold, Edmund Kostewicz, Britta I. Polentarutti, Anna-Lena Ungell, Jennifer B. Dressman

ABSTRACT

PURPOSE: To study the influence of GI hydrodynamics and drug particle size on felodipine absorption in the dog. METHODS: Labradors fistulated at midjejunum were used to selectively study the influence of hydrodynamics and particle size on the in vivo dissolution and absorption of the poorly soluble, lipophilic drug felodipine. A combination of infusion and oral administration of either normal saline or a 5% glucose solution was used to maintain "fasted" and establish "fed" state motility patterns, respectively. The absorption characteristics of both a micronized (8 microm) and a coarse fraction (125 micom) of felodipine were subsequently studied under these two motility patterns. RESULTS: A reduction in particle size led up to an approximate 22-fold increase in maximum plasma concentration and up to an approximate 14-fold increase in area under the curve, with a commensurate decrease in the time at which the maximum plasma concentration occurred. Although the absorption of felodipine from the solution and micronized suspension was not influenced by a change in the hydrodynamics, felodipine was absorbed from the coarse suspension almost twice as well in the "fed" state as under "fasted" conditions. CONCLUSIONS: Absorption from coarse suspensions of felodipine was sensitive to luminal hydrodynamics, whereas micronized suspensions were not. However, the particle size seems to have a much more important influence on the bioavailability of felodipine than the hydrodynamics per se. More... »

PAGES

42-46

References to SciGraph publications

  • 1998-06. Gastric juice as a dissolution medium: Surface tension and pH in EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
  • 1962-02. Effect of Particle Size on Blood Griseofulvin-Levels in Man in NATURE
  • 1975-09. Effect of particle size on the bioavailability of digoxin in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • Identifiers

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    http://scigraph.springernature.com/pub.10.1023/a:1013651215061

    DOI

    http://dx.doi.org/10.1023/a:1013651215061

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001823445

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11837699


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