Pharmacological modulation of metabolic and transport processes: A valuable tool for improving anthelmintic efficacy?

VIVIANI, P.; VIRKEL, G.; LUQUE, S.; LLOBERAS, M.; LANUSSE, C.; LIFSCHITZ, A.

Wroclaw

Congreso; 14th. International Congress of the European Association for Veterinary Pharmacology and Toxicology; 2018

EAVPT

IntroductionIn vivo modulation of drug metabolizing enzymes and transporters may delay the elimination and enhance the systemic availability of anthelmintic compounds. Parasite exposure to the active molecules can be enhanced through their combination with transport modulators or other active anthelmintics. However, the practical relevance of such interactions is unknown. This work aims at assessing the occurrence of PK/PD interactions between (a) oxfendazole and triclabendazole; (b) moxidectin and loperamide; and (c) abamectin and ivermectin/itraconazole in lambs.Materials and MethodsLambs parasitized with nematodes highly resistant to benzimidazole and macrocyclic lactones were used.Experiment 1: Lambs (three groups, n=7 each) were treated with oxfendazole (5 mg/kg PO), triclabendazole (12 mg/kg PO) or their combination;Experiment 2: Lambs (two groups, n=7 each) were treated with moxidectin (0.2 mg/kg SC) alone or in combination with loperamide (0.16 mg/kg PO) and pluronic 123;Experiment 3: Lambs (two groups, n=10 each) were treated with abamectin (0.2 mg/kg SC) alone or in combination with ivermectin (0.2 mg/kg SC) and itraconazole (30 mL PO). Drug/metabolite concentrations in plasma were measured (days 0-15). The faecal egg count reduction test (FECRT) was used as a measure of nematodicidal efficacy.ResultsExperiment 1: Coadministration resulted in an increase in both the plasma AUC0-LOQ and MRT of the metabolite fenbendazole sulfone (p