INVESTIGADORES
ALVAREZ Luis Ignacio
congresos y reuniones científicas
Título:
Evaluation of albendazole disposition
Autor/es:
MORENO, L.; BISTOLETTI, M.; ALVAREZ, L.; LANUSSE, C.
Lugar:
Leipzig, Alemania
Reunión:
Congreso; 11th International Congress of the European Association for Veterinary Pharmacology and Toxicology; 2009
Institución organizadora:
European Association for Veterinary Pharmacology and Toxicology
Resumen:
Introduction Benzimidazole (BZD) anthelmintics are widely used in veterinary medicine. They have broad spectrum, being effective against gastrointestinal roundworms, gapeworms and tapeworms. Endoparasites are a common, and frequently underestimated, problem in avian farms [1]. Flubendazole (FLBZ) is the unique BZD licensed for used in poultry [2]. However, there are evidences that other members of the BZD group such as albendazole (ABZ) and fenbendazole (FBZ) are currently used in poultry. The pharmacokinetic (PK) behaviour and tissue residue depletion for these anthelmintics are well known in ruminant species. However, the available information on BZD PK properties in poultry is scarce. The aims of the current work were: 1) To develop/validate a multiresidue HPLC method to quantify several BZD anthelmintics in hens plasma and eggs 2) To characterise the plasma disposition kinetics and egg residual concentrations of ABZ and its metabolites after oral treatment in laying hens, using  the validated HPLC methodology. Matherial and Methods The developed analytical method included the separation of ten BZD molecules in a same chromatogram: ABZ and its metabolites [ABZ-sulphoxide (ABZSO), ABZ-sulphone (ABZSO2), ABZ-aminosulphone (ABZSO2NH2); FBZ and its metabolites [FBZ-sulphoxide (FBZSO), FBZ-sulphone (FBZSO2)]; FLBZ and its metabolites [FLBZ-hydrolised (FLBZ-H), FLBZ-reduced (FLBZ-R)] and oxibendazole (OBZ) (internal standard). The quantification was realized by HPLC with UV detection (292 nm). A mobile phase composed by ammonium acetate and acetonitrile pumped with a gradient elution at 1.2 ml/min was used. The HPLC separation was performed on a reverse phase C18 (250x4.6 mm, 5 µm) column. A liquid-liquid extraction process was used to recover drug molecules from plasma and eggs. The validation process was carried out following international standards, including selectivity, linearity, stability, precision, accuracy, recovery, limits of detection and quantification. Additionally, six laying hens were orally treated with ABZ (10 mg/kg). Blood samples (72 h) and eggs (8 days) were collected after ABZ treatment. Plasma and egg samples were analysed using the validated methodology.   Results The developed HPLC method allows the simultaneous quantification of up to ten BZD molecules in plasma and egg from laying hens. All validation parameters assayed fell within the accepted range. Concentrations of ABZ and its metabolites (ABZSO and ABZSO2) were measured in plasma after ABZ administration to laying hens. ABZ was rapidly depleted from the bloodstream, being only low levels measurable up to 10 h post-treatment. ABZSO and ABZSO2 were recovered in plasma up to 25 and 30 h post-administration, respectively. An earlier Tmax (P<0.05) was obtained for ABZSO compared to ABZSO2.  A similar plasma AUC value was observed for both metabolites. Residues of ABZ parent drug were not measurable in eggs. The residual concentrations of ABZSO and ABZSO2 in eggs resulted much lower than those found in the bloodstream. The highest residual concentration for ABZSO (0.46 µg/g) and ABZSO2 (0.36 µg/g) were measured at day 2 post-ABZ administration. Discussion The developed methodology may greatly contribute to have a low cost, easy and rapid multiresidue screening procedure for BZD anthelmintics in poultry. The observed excellent resolution for up to ten (10) BZD molecules within the same chromatogram is encouraging. Although differently to other animal species, low ABZ concentrations were detected in the bloodstream in treated hens, the parent drug did not reach the eggs in measurable concentrations. ABZ metabolites were the main residual products recovered in eggs from treated laying hens, reflecting the kinetic pattern observed in the bloodstream.