PT  - JOURNAL ARTICLE
AU  - Gracia Merino
AU  - Ana I. Alvarez
AU  - Julio G. Prieto
AU  - Richard B. Kim
TI  - The Anthelminthic Agent Albendazole Does Not Interact with P-Glycoprotein
AID  - 10.1124/dmd.30.4.365
DP  - 2002 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 365--369
VI  - 30
IP  - 4
4099  - http://dmd.aspetjournals.org/content/30/4/365.short
4100  - http://dmd.aspetjournals.org/content/30/4/365.full
SO  - Drug Metab Dispos2002 Apr 01; 30
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics