The anthelminthic agent albendazole does not interact with p-glycoprotein.
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.
Merino
Gracia
G
Department of Physiology, Faculty of Veterinary, University of Leon, Leon, Spain.
Alvarez
Ana I
AI
Prieto
Julio G
JG
Kim
Richard B
RB
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015766:Albendazole / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004077:Digoxin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018374:LLC-PK1 Cells; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011802:Quinidine / Q000494:pharmacology; D013552:Swine; D014018:Tissue Distribution; D014700:Verapamil / Q000494:pharmacology; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D015766:Albendazole; D000871:Anthelmintics; D002121:Calcium Channel Blockers; D004077:Digoxin; D004791:Enzyme Inhibitors; D011802:Quinidine; D014700:Verapamil; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C095122:multidrug resistance protein 3