The anthelminthic agent albendazole does not interact with p-glycoprotein.

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.