INVESTIGADORES
ALVAREZ Luis Ignacio
artículos
Título:
Comparative drug systemic exposure and clinical efficacy against resistant nematodes in lambs treated with different albendazole formulations.
Autor/es:
SUAREZ, G.; ALVAREZ, L.; CASTELLS, D.; CORREA, O.; FAGIOLINO, P.; LANUSSE, C
Revista:
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2011 vol. 34 p. 557 - 564
ISSN:
0140-7783
Resumen:
A pharmaco-parasitological assessment of four different albendazole (ABZ)
formulations was carried out in lambs infected with multiple resistant
gastrointestinal (GI) nematodes. The comparative drug systemic exposure
profiles (ABZ sulphoxide plasma concentrations) and anthelmintic efficacies
(clinical endpoint measured through the faecal nematode eggs reduction
counts) were determined for a reference formulation (RF) and three different
test (T1, T2, T3) generic ABZ preparations. Fifty (50) Corriedale lambs
naturally infected with multiple resistant GI nematodes were allocated into five
experimental groups (n = 10). Animals in each group received treatment with
either the RF, one of the test ABZ formulations (5 mg⁄ kg by the intraruminal
route) or were kept as untreated control. Blood samples were collected over
48 h post-treatment. ABZ parent drug was not recovered in the bloodstream.
The ABZ sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites were
measured in plasma by ultraviolet high-performance liquid chromatography
over 3648 h post-treatment. A faecal nematode egg count reduction test
(FECRT) was performed at day 10th post-treatment to lambs from all treated
and untreated groups, which indicated the predominance of nematodes with
high level of resistance to ABZ. Both ABZSO Cmax and AUC0LOQ values obtained
for the RF (pioneer product) were significantly higher (P < 0.05) than those
obtained for the T1 and T3 preparations. Based on the currently available
bioequivalence criteria, the test (generic) ABZ formulations under evaluation
could not be considered equivalent to the RF regarding the rate (Cmax) and
extent (AUC0LOD) of drug absorption (indirectly estimated through the ABZSO
metabolite). A large variation in nematode egg counts did not permit to obtain
statistically significant differences among formulations. However, a favourable
trend in the efficacy against the most resistant nematodes was observed for the
formulations with the highest ABZSO systemic exposure.