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Research ArticleArticle

Pulmonary Delivery of Intratracheally Instilled and Aerosolized Cyclosporine A to Young and Adult Rats

Witold Taljanski, Stefan G. Pierzynowski, Pal D. P. Lundin, Björn R. Weström, Stefan Eirefelt, Jerzy Podlesny, Magnus Dahlbäck, Henryka Siwinska-Golebiowska and Börje W. Karlsson
Drug Metabolism and Disposition August 1997, 25 (8) 917-920;
Witold Taljanski
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Stefan G. Pierzynowski
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Pal D. P. Lundin
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Björn R. Weström
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Stefan Eirefelt
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Jerzy Podlesny
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Magnus Dahlbäck
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Henryka Siwinska-Golebiowska
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Börje W. Karlsson
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Abstract

The delivery and pharmacokinetics of cyclosporine A (CyA) given locally to the airways or iv was evaluated in young and adult rats. After intratracheal (i.t.) instillation of saline suspended CyA to adult rats, the CyA plasma levels peaked at 30 min with a bioavailability of 78.1 ± 6.9%. After the i.t. instillation of CyA with micelles forming surfactant, Cremophor EL, in adult and young rats, the plasma levels peaked at 5 min with a bioavailability of 77.5 ± 7.2% and 66.3 ± 4.5%, respectively. The bioavailability of aerosolized CyA was 80.1 ± 4.1% in adults. Thus, CyA is absorbed by the lungs into the systemic circulation of the rat in high amounts, independent of age and type of delivery system. Long-term treatment with i.t. instillations did not affect body weight gain in young and adult rats, and no histopathological changes were found in the lungs. It is important to emphasize that CyA plasma clearance in young rats was lower and elimination half-life longer than in adults. The slow elimination of CyA in young rats indicated profound pharmacokinetic age differences for this species.

Footnotes

  • Send reprint requests to: Dr. Witold Taljanski, Department of Immunology, National Research Institute of Mother and Child, Kasprzaka 17A, 01–211 Warsaw, Poland. E-mail:insmatki{at}warman.com.pl.

  • Grants from the Astra Draco (Lund), Swedish Agricultural Research Council and the Royal Physiographic Society of Lund are gratefully acknowledged.

  • Abbreviations used are::
    CyA
    cyclosporine A
    i.t.
    intratracheal
    BW
    body weight
    Cmax
    peak concentration
    Tmax
    time of peak concentration
    F
    bioavailability
    CL
    plasma total body clearance
    Varea
    apparent volume of distribution
    Vss
    steady state volume of distribution
    MRT
    mean residence time
    • Received October 21, 1996.
    • Accepted March 12, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition
Vol. 25, Issue 8
1 Aug 1997
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Research ArticleArticle

Pulmonary Delivery of Intratracheally Instilled and Aerosolized Cyclosporine A to Young and Adult Rats

Witold Taljanski, Stefan G. Pierzynowski, Pal D. P. Lundin, Björn R. Weström, Stefan Eirefelt, Jerzy Podlesny, Magnus Dahlbäck, Henryka Siwinska-Golebiowska and Börje W. Karlsson
Drug Metabolism and Disposition August 1, 1997, 25 (8) 917-920;

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Research ArticleArticle

Pulmonary Delivery of Intratracheally Instilled and Aerosolized Cyclosporine A to Young and Adult Rats

Witold Taljanski, Stefan G. Pierzynowski, Pal D. P. Lundin, Björn R. Weström, Stefan Eirefelt, Jerzy Podlesny, Magnus Dahlbäck, Henryka Siwinska-Golebiowska and Börje W. Karlsson
Drug Metabolism and Disposition August 1, 1997, 25 (8) 917-920;
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