Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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The Effect of Protein Restriction in the In Vitro Metabolism of Albendazole in Rats

Author(s): Katia Roberta A. Belaz, Josiane de O. Cardoso, Carlos Alberto da Silva, Regina V. Oliveira.

Graphical Abstract:


Abstract:

This work presents an in vitro investigation of the effect of protein restriction on the metabolism of albendazole (ABZ). This study was conducted using liver microsomal fractions obtained from Wistar rats. For the quantitative analysis, a multidimensional High Performance Liquid Chromatography (2D HPLC) method was fully validated for the determination of the ABZ metabolites: albendazole sulfoxide, albendazole sulfone and albendazole 2-aminesulfone.

The target compounds were directly extracted using a C8-RAM-BSA column (5.0 x 0.46 cm i.d.) and analyzed on a chromatographic chiral column containing amylose tris(3,5-dimethylphenylcarbamate) (150 x 4.6 mm i.d.). The in vitro biotransformation results showed that the protein restriction influenced the oxidative metabolism of ABZ. The production of R-(+)-ABZ-SO (1309 nmol/L) and S-(-)-ABZ-SO (1456 nmol/L) was higher in the control animals than in the animals fed with a diet containing 6% protein, which produced 778.7 nmol/L and 709.5 nmol/L for R-(+) and S-(-)-ABZ-SO enantiomers, respectively. These results were statistically inspected by Student´s t test and the results showed a significant difference between the two means (p < 0.05). Moreover, the production of ABZ-SO enantiomers was enantioselective where the S-(-)-ABZ-SO was formed in greater amounts than the R-(+)-ABZ-SO in control animals (p = 0.0231). However, the enantioselectivity was not observed when the in vitro biotransformation of ABZ was conducted using the microsomal fractions obtained from protein restriction animals (p > 0.05). Furthermore, animal nutritional condition could affect the pattern of ABZ sulphoxidation indicating that the protein nutrition affect primarily the formation of R-(+)-ABZSO and S-(-)-ABZ-SO enantiomers.

Keywords: Albendazole metabolites, enantioselective metabolism, in vitro metabolism, multidimensional liquid chromatography, protein restriction, rat liver microsomes.

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Article Details

VOLUME: 9
ISSUE: 1
Year: 2015
Page: [8 - 16]
Pages: 9
DOI: 10.2174/1872312809666150401105843