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
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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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