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Studies of pharmacokinetics and therapeutic effects of glucocorticoids entrapped in liposomes after intraarticular application in healthy rabbits and in rabbits with antigen-induced arthritis

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Summary

Dexamethasone palmitate (DMP) entrapped in liposomes of defined sizes was administered intraarticularly in healthy rabbits and in rabbits with antigen-induced arthritis. The pharmacokinetics and therapeutic effect of liposomal DMP were measured and compared with corresponding experiments using microcrystalline triamcinolone acetonide (TAC). The small DMP liposomes (diameter 160 nm) showed a greater decrease in joint circumference than the 3-times-higher dose of microcrystalline TAC. Moreover, about 98% of administered TAC had already disappeared from the joint 6 h after injection, whereas about 36% of liposomal DMP was still measured in synovial fluid and synovium at the same time. Increasing the vesicle diameter from 160 to 750 nm (large liposomes) improved the retention of DMP by a factor of 2.6 within 48 h after injection in healthy rabbits. In addition, none of the liposomal glucocorticoid preparations ever suppressed the endogenous plasma cortisol level, which is in contrast to the suppression measured after administration of the microcrystalline preparation.

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Author notes

  1. M. Stimpel

    Present address: Medizinische Klinik II, Universität Köln, Krankenhaus Merheim, D-5000, Köln 91, Federal Republic of Germany

Authors and Affiliations

  1. Abteilung für Physikalische Pharmazie und Biopharmazie, ETH-Zentrum, Pharmazeutisches Institut, CH-8092, Zürich, Switzerland

    M. H. Bonanomi, K. M. Roos & H. G. Weder

  2. Rheumaklinik, Universitätsspital, CH-8091, Zürich, Switzerland

    M. Velvart & K. Fehr

  3. Medizinische Poliklinik, Hypertonie-Abteilung, Universitätsspital, CH-8091, Zürich, Switzerland

    M. Stimpel

Authors
  1. M. H. Bonanomi
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  2. M. Velvart
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  3. M. Stimpel
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  4. K. M. Roos
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  5. K. Fehr
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  6. H. G. Weder
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Bonanomi, M.H., Velvart, M., Stimpel, M. et al. Studies of pharmacokinetics and therapeutic effects of glucocorticoids entrapped in liposomes after intraarticular application in healthy rabbits and in rabbits with antigen-induced arthritis. Rheumatol Int 7, 203–212 (1987). https://doi.org/10.1007/BF00541378

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  • DOI: https://doi.org/10.1007/BF00541378

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