INVESTIGADORES
ALVAREZ Luis Ignacio
artículos
Título:
Improving the in vitro dissolution rate and pharmacokinetic performance of fenbendazole in sheep using drug nanocrystals
Autor/es:
MELIAN, MARÍA ELISA; IBARRA, MANUEL; CEBALLOS, LAURA; PAREDES, ALEJANDRO J.; MUNGUÍA, BEATRIZ; FACCIO, RICARDO; PALMA, SANTIAGO; ÁLVAREZ, LUIS IGNACIO; DOMÍNGUEZ, LAURA
Revista:
RESEARCH IN VETERINARY SCIENCE
Editorial:
ELSEVIER SCI LTD
Referencias:
Año: 2022 vol. 142 p. 110 - 116
ISSN:
0034-5288
Resumen:
Benzimidazole methylcarbamate anthelmintics, including fenbendazole (FBZ), have only limited water solubility and small differences in drug solubility may have a major influence on their absorption, pharmacokinetic behavior and anthelmintic efficacy. To improve FBZ water solubility and dissolution rate, novel self-dispersible nanocrystals (SDNCs) of FBZ were recently described. In this work, the pharmacokinetic behavior of the SDNCs of FBZ and Poloxamer 188 was compared against a physical mixture (PM) of its components. The experiment was conducted following a crossover design with two different experimental phases. In phase I, sheep were treated with the SDNC (n = 3) or the PM (n = 3) formulations by the intraruminal route at the same dose rate (5 mg/kg). The treatment groups were reversed after a 7-days washout period. A non-compartmental analysis of the concentration in plasma versus time results showed that the calculated Cmax and AUC0-T were significantly higher (p < 0.05) for FBZ and its metabolites after the SDNC treatment compared to the PM (for FBZ: Cmax 0.346 μg/mL and AUC0-T 10.1 μg.h/mL after the SDNC vs Cmax 0.157 μg/mL and AUC0-T 5.1 μg.h/mL after the PM treatment). Additionally, population pharmacokinetic parameters of FBZ were estimated for the first time in sheep. In conclusion, the formulation of FBZ as SDNCs is a promising approach to improve FBZ dissolution reaching a higher drug plasma exposure in ruminants.