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Research ArticleArticle

RENAL-SELECTIVE DELIVERY AND ANGIOTENSIN-CONVERTING ENZYME INHIBITION BY SUBCUTANEOUSLY ADMINISTERED CAPTOPRIL-LYSOZYME

Jai Prakash, Annemiek M. van Loenen-Weemaes, Marijke Haas, Johannes H. Proost, Dirk K. F. Meijer, Frits Moolenaar, Klaas Poelstra and Robbert J. Kok
Drug Metabolism and Disposition May 2005, 33 (5) 683-688; DOI: https://doi.org/10.1124/dmd.104.002808
Jai Prakash
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Annemiek M. van Loenen-Weemaes
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Marijke Haas
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Johannes H. Proost
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Dirk K. F. Meijer
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Frits Moolenaar
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Klaas Poelstra
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Robbert J. Kok
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Abstract

In previous studies, we have demonstrated that the low molecular weight protein lysozyme can be used as a renal-selective drug carrier for delivery of the angiotensin-converting enzyme (ACE) inhibitor captopril. Typically, such macromolecular drug-targeting preparations are administered intravenously. In the present study, we investigated the fate of captopril-lysozyme following subcutaneous administration, a convenient route for long-term treatment. The absorption from the subcutaneous injection site and renal uptake of lysozyme were determined by gamma scintigraphy in rats. Bioavailability, renal accumulation, and stability of the captopril-lysozyme conjugate were evaluated by high performance liquid chromatography analysis and by ACE activity measurements. Lysozyme was absorbed gradually and completely from the subcutaneous injection site within 24 h and accumulated specifically in kidneys. After subcutaneous injection of the captopril-lysozyme conjugate, higher renal captopril levels and lower captopril-lysozyme levels in urine indicated the improved renal accumulation in comparison with intravenous administration of the conjugate, as well as its stability at the injection site. After both treatments, captopril-lysozyme conjugate effectuated renal ACE inhibition, whereas plasma ACE was not inhibited. In conclusion, our results demonstrate that we can use the subcutaneous route to administer drug delivery preparations like the captopril-lysozyme conjugate.

Footnotes

  • Part of the present work has been presented as a poster at the Eighth European Symposium on Controlled Drug Delivery, April 7–9, 2004, Noordwijk, The Netherlands.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.104.002808.

  • ABBREVIATIONS: LMWP, low-molecular-weight protein; ACE, angiotensin-converting enzyme; HPLC, high performance liquid chromatography; TC, tyramine cellobiose; AIC, Akaike's information criterion; AUC, area under the curve.

    • Received October 29, 2004.
    • Accepted January 25, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 33 (5)
Drug Metabolism and Disposition
Vol. 33, Issue 5
1 May 2005
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Research ArticleArticle

RENAL-SELECTIVE DELIVERY AND ANGIOTENSIN-CONVERTING ENZYME INHIBITION BY SUBCUTANEOUSLY ADMINISTERED CAPTOPRIL-LYSOZYME

Jai Prakash, Annemiek M. van Loenen-Weemaes, Marijke Haas, Johannes H. Proost, Dirk K. F. Meijer, Frits Moolenaar, Klaas Poelstra and Robbert J. Kok
Drug Metabolism and Disposition May 1, 2005, 33 (5) 683-688; DOI: https://doi.org/10.1124/dmd.104.002808

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Research ArticleArticle

RENAL-SELECTIVE DELIVERY AND ANGIOTENSIN-CONVERTING ENZYME INHIBITION BY SUBCUTANEOUSLY ADMINISTERED CAPTOPRIL-LYSOZYME

Jai Prakash, Annemiek M. van Loenen-Weemaes, Marijke Haas, Johannes H. Proost, Dirk K. F. Meijer, Frits Moolenaar, Klaas Poelstra and Robbert J. Kok
Drug Metabolism and Disposition May 1, 2005, 33 (5) 683-688; DOI: https://doi.org/10.1124/dmd.104.002808
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