Modulation of intestinal P. glycoprotein activity on the ivermectin absortion is affected by the administration route in sheep.

BALLENT M., LIFCHITZ A., VIRKEL G., SALLOVITZ J., SCARCELLA S., & LANUSSE C.

Cordoba, Argentina

Congreso; XXXVIII Congreso de la Sociedad Argentina de Farmacología Experimental; 2006

Ivermectin (IVM), a broad-spectrum antiparasitic drug used in veterinary and human medicine, has been shown to be a substrate of the drug transport P-glycoprotein (P-gp). The aim of the study was to assess the comparative impact of the itraconazole (ITZ)- mediated modulation of the intestinal P-gp activity on the kinetic behaviour of IVM administered by the intravenous (IV) and intraruminal (IR) routes to sheep. Adult female Corriedale sheep were allocated into four groups. Animals (n=20) received IVM (50µg/Kg) by IV route either alone (Group A) or co-administered with ITZ (100 mg, 3 doses, orally) (Group B). Animals in Groups C and D (n=24) were IR-treated with IVM alone or with ITZ, respectively. Plasma was collected up to 15 days post-treatment. Twelve (12) IVM IR-treated sheep, with and without ITZ, were sacrificed to collect the mucosal tissue and luminal content of different gastrointestinal tract sections. IVM concentrations were measured by HPLC. The plasma disposition kinetics of IVM given IV was unaffected by the presence of ITZ. However, the IR administration of IVM+ITZ resulted in markedly higher IVM bioavailability compared to the IVM alone treatment. Likewise, the IVM concentration was enhance in different gastrointestinal mucosal tissues in the presence of the P-gp modulator agent.