IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Pharmacokinetics of a microcrystalline albendazole formulation orally administered to CBi-IGE mice
Autor/es:
VASCONI, M. D.; HINRICHSEN, L.; PRIOTTI, J.; LAMAS, M. C.; CODINA, A. V.; LEONARDI, D.
Lugar:
Rosario
Reunión:
Congreso; IV Reunión Internacional de Ciencias Farmacéuticas RICIFA; 2016
Resumen:
Albendazole (ABZ) is an anthelmintic compound widely used in the treatment of nematode infections. Its effectiveness is limited by its poor water solubility and low bioavailability. To improve its solubility, controlled precipitation using stabilizer polymers such as cellulose and chitosan, followed by spray drying, was employed to prepare ABZ microcrystals. These formulations were thoroughly characterized physicochemically (yield, dissolution efficiency, solid state analysis by XRD, DSC, and SEM), and their in vitro parasiticidal activity against T. spiralis evaluated, to select the best for in vivo studies. The aim of this work was to assess whether the selected chitosan-based microcrystal, S10A improves ABZ pharmacokinetics in mice. The assay was performed in CBi/L mice (mean BW 30 g) given an oral dose of 30 mg ABZ/kg as pure drug or S10A. Blood samples were collected into heparinized vials at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 and 24 h after drug administration and centrifuged to obtain plasma. After the extraction process, the samples were frozen until high-performance liquid chromatography (HPLC) analysis. Albendazole sulphoxide, the main metabolite, was identified by comparison with retention times of a pure reference standard. The variables studied were Tmax (time to achieve Cmax, h) and Cmax (maximum plasma concentration, µg/mL). The area under the concentration-time curve from 0 to 24 h (AUC, µg h/mL) was calculated using the trapezoidal rule method. Males and females given S10A showed an increased Cmax compared to mice administered ABZ (♂, CmaxABZ=3,26, CmaxS10A=5,73; ♀, CmaxABZ=4,93, CmaxS10A=6,83); Cmax was detected at the same time in both groups (Tmax=1 h). Compared with ABZ, S10A increased AUC 113% in males and 54% in females. Sex-related differences in gastrointestinal physiology may explain the observed responses. The results indicate that the methodology improved the systemic availability of the drug, and a better therapeutic efficacy should be expected.