Feeding Management and Albendazole Pharmacokinetics in Pigs

Alvarez Luis Ignacio, Chiappetta Valentina, Moriones Lucila, Dominguez Paula, Canton Candela,Lanusse Carlos, Ceballos Laura

ANIMALS(2023)

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摘要
Simple Summary Helminth parasite infections have a significant impact on the efficiency of swine production as a consequence of the reduced feed conversion and weight gain and the condemnation of affected organs after slaughter. Parasite control is primarily based on the use of chemical agents, such as albendazole, a broad-spectrum benzimidazole anthelmintic compound. After oral administration, the dissolution and absorption of albendazole may be significantly modified by the type of diet, which may induce substantial variation in the amounts of the active drug/metabolites that actually reach the parasite to exert the anthelmintic action. This diet-related variability may have relevant implications on the drug efficacy, affecting the overall success of parasite control programs. Herein, we describe the relationship between the feeding management and the pharmacokinetic behavior of albendazole in pigs. Although the type of diet did not result in a significant difference in the systemic exposure to albendazole/metabolites, the higher fat content in the diet (by the addition of soya oil) was correlated with higher albendazole sulfoxide concentrations 12 h post-treatment. Albendazole (ABZ) is a methylcarbamate benzimidazole anthelmintic used to control gastrointestinal parasites in several animal species and humans. The type of diet has been identified as a major determinant for ABZ pharmacokinetics in different animal species and humans. The work described here assesses the pattern of the absorption and the systemic availability of ABZ and its metabolites after its oral administration to pigs under different feed management plans. Eighteen pigs (5 months old, local ecotype breeds) were distributed into three experimental groups. In the fasting group, the animals fasted for 8 h prior to treatment. In the pellet + oil and pellet groups, the animals were fed ad libitum with a commercial pelleted-based diet with or without the addition of soya oil. An ABZ suspension was orally administered at 10 mg/kg. Blood samples were taken over the 48 h post-treatment. The plasma samples were analyzed by HPLC. Under the described experimental conditions, the ingestion of the pellet-based diet with or without the soya oil before ABZ treatment did not significantly (p < 0.05) modify the plasma disposition kinetics of the ABZ sulfoxide (ABZSO, the main ABZ metabolite) compared to that observed in the fasting pigs. Both ABZ metabolites (ABZSO and ABZ sulphone) reached similar peak concentrations and systemic exposures in all the experimental groups regardless of the feeding management. However, the addition of oil to the pelleted food enhanced the pattern of ABZ absorption, which was reflected in the higher (p < 0.05) concentration profiles of the active ABZSO metabolite measured between 12 and 48 h post-treatment compared to the pigs fed with the pelleted food alone. Although this effect may not be therapeutically relevant after ABZ administration as a single oral dose, the overall impact of the type and feeding conditions when ABZ is supplemented with food for several days should be cautiously evaluated.
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关键词
albendazole,pharmacokinetics,systemic exposure
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