Phytochemicals in Gastrointestinal Nematode Control: Pharmacokinetic–Pharmacodynamic Evaluation of the Ivermectin plus Carvone Combination

MIRÓ, MARÍA VICTORIA; COSTA-JÚNIOR, LIVIO MARTINS; LLOBERAS, MARÍA MERCEDES; CARDOZO, P.; LANUSSE, CARLOS EDMUNDO; VIRKEL G; LIFSCHITZ A

Animals

Multidisciplinary Digital Publishing Institute

Lugar: Basilea; Año: 2023 vol. 13 p. 1 - 14

2076-2615

Abstract: A wide variety of plant-derived phytochemicals with anthelmintic effects have been described. Most of them have shown activity against parasites in vitro but have not been extensivelyexplored in vivo. The aim of the current work was to study the pharmacokinetic–pharmacodynamicrelationship of the combined administration of carvone (R-CNE) and ivermectin (IVM) to lambs.Three trials were conducted to evaluate the pharmacological interaction between R-CNE and IVM inlambs infected with resistant nematodes. Drug concentrations were measured in plasma, target tissues, and H. contortus by HPLC with fluorescent (IVM) and ultraviolet (R-CNE) detection. The effectof both compounds on parasites was estimated by the fecal egg count reduction. Coadministrationwith R-CNE significantly increased the plasma bioavailability of IVM. R-CNE showed a moderateanthelmintic effect, which was greater on the susceptible isolate of H. contortus. After the combinationof R-CNE and IVM as an oral emulsion, both compounds were quantified in H. contortus recoveredfrom infected lambs. However, R-CNE concentrations were much lower than those reported toachieve anthelmintic effects in the in vitro assays. Optimization of the pharmaceutical formulation,dose rate, and administration schedule is needed to take advantage of the intrinsic anthelminticactivity of phytochemicals