Enhanced absorption of pour-on ivermectin formulation in rats by co-administration of the multidrug-resistant-reversing agent verapamil.
The effect of verapamil, a multidrug-resistance (Mdr)-reversing agent on the absorption of a pour-on formulation of ivermectin was evaluated in rats. Absorption of ivermectin was effectively enhanced (40%) by the presence of verapamil, suggesting that absorption of ivermectin involves Mdr-P-glycoprotein and that verapamil should act as a competitive inhibitor for the transport and extrusion of ivermectin by P-glycoprotein. This hypothesis is consistent with other studies describing verapamil as a blocking agent of P-glycoprotein involved in the efflux of ivermectin in a resistant strain of Haemonchus contortus.
Alvinerie
M
M
Laboratoire de Pharmacologie-Toxicologie, INRA, Toulouse, France. malviner@toulouse.inra.fr
Dupuy
J
J
Eeckhoutte
C
C
Sutra
J F
JF
D000042:Absorption; D000279:Administration, Cutaneous; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D007559:Ivermectin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D014700:Verapamil / Q000008:administration & dosage*
D000871:Anthelmintics; D007559:Ivermectin; D014700:Verapamil