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Research ArticleArticle

Presystemic Metabolism of Albendazole: Experimental Evidence of an Efflux Process of Albendazole Sulfoxide to Intestinal Lumen

P. A. Redondo, A. I. Álvarez, J. L. Garcia, O. M. Larrodé, G. Merino and J. G. Prieto
Drug Metabolism and Disposition June 1999, 27 (6) 736-740;
P. A. Redondo
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A. I. Álvarez
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J. L. Garcia
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O. M. Larrodé
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G. Merino
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J. G. Prieto
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Abstract

Albendazole (ABZ) presystemic clearance was studied in rat by perfusion of a 25 μM ABZ solution in isolated intestinal loops. Significant secretion of the active metabolite, ABZSO, into the lumen was observed. The metabolite was also present in mesenteric blood. After 30 min of intestinal perfusion, 64% of the ABZ dose had disappeared from lumen. The total amount of ABZSO measured was 0.341 ± 0.04 nmol/cm with 0.176 ± 0.03 nmol/cm in mesenteric blood. The metabolite secretion to intestinal lumen was 0.165 ± 0.05 nmol/cm. Intestinal sulfoxidation was induced by repeated administration of ABZ and ABZ coadministered with surfactants, especially polysorbate 80. The enantioselectivity of the in vitro intestinal sulfoxidation of ABZ showed that the relative contribution of P-450 and flavin-containing monooxygenase was quite similar, but after the induction by ABZ coadministered with polysorbate 80, the cytochrome P-450 system contribution was significantly increased. The appearance of ABZSO in mesenteric blood clearance was also increased under these conditions.

Footnotes

  • Send reprint requests to: Julio G. Prieto, Laboratory of Animal Physiology, Faculty of Veterinary, University of León, E24071, León, Spain. E-mail: dfijpf{at}unileon.es

  • This work was supported by Comision Interministerial de Ciencia y Tecnologia (CICYT) (Spain) (FAR 91/0748 project).

  • Abbreviations used are::
    ABZ
    albendazole
    ABZSO
    albendazole sulfoxide
    ABZSO2
    albendazole sulfone
    e.e.
    enantiomeric excess
    • Received April 2, 1998.
    • Accepted March 1, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 27 (6)
Drug Metabolism and Disposition
Vol. 27, Issue 6
1 Jun 1999
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Research ArticleArticle

Presystemic Metabolism of Albendazole: Experimental Evidence of an Efflux Process of Albendazole Sulfoxide to Intestinal Lumen

P. A. Redondo, A. I. Álvarez, J. L. Garcia, O. M. Larrodé, G. Merino and J. G. Prieto
Drug Metabolism and Disposition June 1, 1999, 27 (6) 736-740;

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Research ArticleArticle

Presystemic Metabolism of Albendazole: Experimental Evidence of an Efflux Process of Albendazole Sulfoxide to Intestinal Lumen

P. A. Redondo, A. I. Álvarez, J. L. Garcia, O. M. Larrodé, G. Merino and J. G. Prieto
Drug Metabolism and Disposition June 1, 1999, 27 (6) 736-740;
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