title: Combined use of ivermectin and triclabendazole in sheep: in vitro and in vivo characterisation of their pharmacological interaction.
abstract: This study evaluated the pharmacokinetic properties of ivermectin (IVM) and triclabendazole (TCBZ) given either separately or co-administered to sheep. Corriedale sheep received IVM alone, TCBZ alone or a combination of IVM and TCBZ intravenously. Ivermectin elimination was delayed and its plasma availability was 3-fold higher when co-administered with TCBZ. Similarly, plasma concentrations of TCBZ and its metabolites were influenced by the co-administration of IVM. Higher peak plasma concentrations of TCBZ metabolites were detected after the co-administration of TCBZ and IVM compared to those obtained following TCBZ treatment in isolation. Complementary in vitro assays were carried out to assess the influence of TCBZ on the P-glycoprotein-mediated intestinal transport of IVM, using the everted gut sac technique. Enhanced accumulation of IVM in the intestinal wall occurred after co-incubation with TCBZ.
authors.affiliation: Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Campus Universitario, 7000 Tandil, Argentina. adrianl@vet.unicen.edu.ar
authors.forename: Adrian
authors.initials: A
authors.lastname: Lifschitz
authors.forename: Guillermo
authors.initials: G
authors.lastname: Virkel
authors.forename: Mariana
authors.initials: M
authors.lastname: Ballent
authors.forename: Juan
authors.initials: J
authors.lastname: Sallovitz
authors.forename: Carlos
authors.initials: C
authors.lastname: Lanusse
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007422:Intestines / Q000187:drug effects*; D007559:Ivermectin / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D012756:Sheep / Q000378:metabolism*; D000077682:Triclabendazole
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000871:Anthelmintics; D001562:Benzimidazoles; D000077682:Triclabendazole; D007559:Ivermectin