Changes to oxfendazole chiral kinetics and anthelmintic efficacy induced by piperonyl butoxide in horses.
BACKGROUND
The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs.


OBJECTIVE
To evaluate the effects of piperonyl butoxide (PB) (a metabolic inhibitor) 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 naturally parasitised crossbred male ponies were allocated into 3 groups (n = 5) and treated orally as follows: Group I (control) received distilled water as placebo; Group II was dosed with OFZ (10 mg/kg bwt); and Group III was treated with OFZ (10 mg/kg bwt) co-administered with PB (63 mg/kg bwt). Jugular blood samples were obtained over 120 h post treatment. Three weeks after treatments, all experimental horses were subjected to euthanasia.


RESULTS
The observed maximum plasma concentration (Cmax) and area under the concentration vs. time curve (AUC) values for OFZ increased 3- and 5-fold, respectively, in the presence of PB. The plasma concentration profiles of fenbendazole (FBZ), a metabolite generated from OFZ, were significantly lower after the treatment with OFZ alone (AUC = 0.8 microg x h/ml) compared to those obtained after the OFZ + PB treatment (AUC = 2.7 microg x h/ml). The enhanced pharmacokinetic profiles correlated with increased anthelmintic efficacy. The combination OFZ + PB showed 100% efficacy against mature nematode parasites. The efficacy against cyathostome L3 larvae increased from 94% (Group II) to 98.7% (Group III). Consistently, the number of L4 larvae recovered from OFZ + PB treated horses (Group III) (n = 146) was significantly lower (P<0.05) than that recovered from Group II (n = 1397).


CONCLUSIONS
The use of PB as a metabolic inhibitor may be useful to enhance OFZ activity against mature and migrating larvae of different parasite species in horses.


CONCLUSIONS
Metabolic inhibitors may be used to enhance the activity of benzimidazole anthelmintics and extend the effective lifespan of benzimidazole drugs in the face of increasing resistance.
Sánchez Bruni
S F
SF
Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Campus Universitario, 7000, Tandil.
Fusé
L A
LA
Moreno
L
L
Saumell
C A
CA
Alvarez
L I
LI
Fiel
C
C
McKellar
Q A
QA
Lanusse
C E
CE
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005243:Feces / Q000469:parasitology; D006734:Horse Diseases / Q000188:drug therapy* / Q000378:metabolism; D006736:Horses; D008297:Male; D010270:Parasite Egg Count / Q000662:veterinary; D010273:Parasitic Diseases, Animal / Q000188:drug therapy* / Q000378:metabolism; D010574:Pesticide Synergists / Q000494:pharmacology* / Q000627:therapeutic use; D010882:Piperonyl Butoxide / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D016896:Treatment Outcome
D000871:Anthelmintics; D001562:Benzimidazoles; D010574:Pesticide Synergists; D010882:Piperonyl Butoxide; C011030:oxfendazole