Changes to oxfendazole chiral kinetics and anthelmintic efficacy induced by piperonyl butoxide in horses.

SÁNCHEZ BRUNI, S., SAUMELL, C., MORENO, L., ALVAREZ, L., FUSÉ, L., FIEL, C.; MCKELLAR, Q., LANUSSE, C

EQUINE VETERINARY JOURNAL

Equine Vet. Journal Ltd.

Lugar: London; Año: 2005 vol. 37 p. 257 - 262

Reasons for performing the study: The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. Objectives: The main goals of the current trials were to evaluate the effects of piperonyl butoxide (PB) on the plasma availability and enantiomeric behaviour of oxfendazole (OFZ) given orally to horses, and to compare the clinical efficacy of OFZ given either alone or co-administered with PB in naturally parasitised horses. Methods: Fifteen (15) naturally parasitised crossbred male ponies were allocated into three (3) groups (n=5) and orally treated as follows: Group I, control (received distilled water as placebo); Group II, was dosed with OFZ (10 mg/kg); and Group III, was treated with OFZ (10 mg/kg) co-administered with PB (63 mg/kg). Jugular blood samples were obtained over 120 h post-treatment. Three (3) weeks after treatments, all the experimental horses were sacrificed. Results: The observed maximum plasma concentration (Cmax) and area under the concentration vs time curve (AUC) values for OFZ parent drug increased 3 and 5-fold, respectively, in the presence of PB. The plasma concentration profiles of the fenbendazole (FBZ), metabolite generated from OFZ, were significantly lower after the treatment with OFZ alone (AUC= 0.8 µg.h/mL) compared to those obtained after the OFZ + PB treatment (AUC= 2.7 µg.h/mL). The enhanced pharmacokinetic profiles correlated with increased anthelmintic efficacy. The combination OFZ + PB showed 100 % efficacy against adult nematode parasites. The efficacy against Cyathostome L3 larvae increased from 94 % (OFZ) to 98.7 % (OFZ + PB). Consistently, the number of L4 larvae recovered from OFZ + PB treated horses (146) was significantly lower (P<0.05) compared to those recovered after the OFZ alone treatment (1397). Conclusions: This work demonstrates that the use of PB as a metabolic inhibitor may be useful to enhance OFZ activity against adult and migrating larvae of different parasite species in horses