title: Evaluation of the interaction between ivermectin and albendazole following their combined use in lambs.
abstract: Mixtures of drugs from different chemical families have been proposed as a valid strategy to delay the development of anthelmintic resistance. The current work summarizes the outcome of the evaluation of the plasma disposition kinetics of albendazole (ABZ) and ivermectin (IVM) administered either alone or co-administered to lambs infected with gastrointestinal (GI) nematodes resistant to both anthelmintic molecules. Thirty six (36) Corriedale lambs naturally infected with multiple resistant GI nematodes were allocated into six treatment groups: (a) ABZ intravenous (ABZ(IV)); (b) IVM(IV); (c) ABZ(IV) + IVM(IV); (d) ABZ intraruminal (IR); (e) IVM subcutaneous (SC) and (f) ABZ(IR) + IVM(SC). Plasma samples were collected over 15 days post-treatment and analysed by HPLC. The estimated pharmacokinetic (PK) parameters were statistically compared using parametric and non-parametric statistical tests. The presence of IVM did not affect the plasma disposition kinetics of ABZ and its metabolites after the i.v. administration. However, the ABZ sulphoxide (ABZSO) area under the concentration vs. time curve (AUC) was significantly lower (P < 0.01) after the intraruminal (i.r.) administration of ABZ alone compared to that obtained for the combined treatment with IVM [subcutaneous (s.c.) injection]. The IVM plasma AUC obtained after its i.v. co-administration with ABZ was 88% higher (P < 0.05) compared to the treatment with IVM alone. Any marked difference on IVM PK parameters was observed between the treatments ABZ + IVM and IVM alone injected subcutaneously. The data obtained here indicate that the co-administration of ABZ and IVM does not induce an adverse kinetic interaction. This type of pharmacology-based evaluation of drug interactions is becoming highly relevant as drug combinations are now widely used as an alternative to control resistant helminth parasites in livestock.
authors.affiliation: Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Alvarez
authors.forename: A
authors.initials: A
authors.lastname: Lifschitz
authors.forename: C
authors.initials: C
authors.lastname: Entrocasso
authors.forename: J
authors.initials: J
authors.lastname: Manazza
authors.forename: L
authors.initials: L
authors.lastname: Mottier
authors.forename: B
authors.initials: B
authors.lastname: Borda
authors.forename: G
authors.initials: G
authors.lastname: Virkel
authors.forename: C
authors.initials: C
authors.lastname: Lanusse
mesh_terms: D015766:Albendazole / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D007559:Ivermectin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008657:Metabolic Clearance Rate; D009349:Nematode Infections / Q000188:drug therapy / Q000662:veterinary*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000871:Anthelmintics; D007559:Ivermectin; D015766:Albendazole