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Rapid CommunicationShort Communication

The Anthelminthic Agent Albendazole Does Not Interact with P-Glycoprotein

Gracia Merino, Ana I. Alvarez, Julio G. Prieto and Richard B. Kim
Drug Metabolism and Disposition April 2002, 30 (4) 365-369; DOI: https://doi.org/10.1124/dmd.30.4.365
Gracia Merino
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Ana I. Alvarez
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Julio G. Prieto
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Richard B. Kim
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Abstract

Albendazole is a clinically important anthelminthic agent known to have variable and low oral bioavailability. The aim of this work was to determine whether albendazole, a CYP3A4 substrate, is also a substrate for the multidrug efflux transporter P-glycoprotein. Both in vitro and in vivo methods were used to assess the role of P-glycoprotein-mediated albendazole transport. In cultured LLC-PK1, L-MDR1, and Caco-2 cells, albendazole was found not to be a P-glycoprotein substrate; the transport across LLC-PK1 and L-MDR1 cells revealed basal to apical versus apical to basal transport to a similar extent. In addition, there was no inhibitory effect of albendazole on digoxin transport in Caco-2 cells, and P-glycoprotein inhibitors (verapamil and quinidine) did not affect transport across Caco-2 cells. The in vivo relevance of P-glycoprotein to albendazole disposition was assessed using mdr1a/1b(−/−) mice after intravenous administration of albendazole (15 mg/kg). A similar pattern of tissue distribution in both P-glycoprotein-deficient and wild-type mice was observed. In conclusion, albendazole is neither a substrate nor an inhibitor of P-glycoprotein. Therefore, interactions between albendazole and P-glycoprotein substrates or inhibitors are unlikely to be clinically important.

Footnotes

  • This work was supported by a United States Public Health Service (USPHS)Grant GM31304 and GM54724 and Grant PN98 9789011G (to G.M.) from Ministry of Science and Technology (Spain), Plan Nacional de Formacion de Personal Investigador.

  • Abbreviations used are::
    ABZ
    albendazole
    ABZSO
    albendazole sulfoxide
    ABZSO2
    albendazole sulfone
    P-gp
    P-glycoprotein
    MDR
    multidrug resistance
    HPLC
    high-pressure liquid chromatography
    cMOAT
    canalicular multispecific organic anion transporter
    • Received October 10, 2001.
    • Accepted January 14, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 30 (4)
Drug Metabolism and Disposition
Vol. 30, Issue 4
1 Apr 2002
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Rapid CommunicationShort Communication

The Anthelminthic Agent Albendazole Does Not Interact with P-Glycoprotein

Gracia Merino, Ana I. Alvarez, Julio G. Prieto and Richard B. Kim
Drug Metabolism and Disposition April 1, 2002, 30 (4) 365-369; DOI: https://doi.org/10.1124/dmd.30.4.365

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Rapid CommunicationShort Communication

The Anthelminthic Agent Albendazole Does Not Interact with P-Glycoprotein

Gracia Merino, Ana I. Alvarez, Julio G. Prieto and Richard B. Kim
Drug Metabolism and Disposition April 1, 2002, 30 (4) 365-369; DOI: https://doi.org/10.1124/dmd.30.4.365
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