Albendazole metabolism in patients with neurocysticercosis: antipyrine as a multifunctional marker drug of cytochrome P450

Brazilian Journal of Medical and Biological Research

M.p. Marques²  O.m. Takayanagui¹  V.l. Lanchote² 

[1] ,Universidade de São Paulo Faculdade de Ciências Farmacêuticas de Ribeirão Preto Departamento de Análises Clínicas, Toxicológicas e BromatológicasRibeirão Preto SP ,Brasil

关键词: Albendazole;    Cysticercosis;    Enantiomers;    Antipyrine;    Cytochrome P450;    CYP;    Patients;   

DOI  :  10.1590/S0100-879X2002000200016

来源: SciELO

【 摘 要 】

The present study investigates the isoform(s) of cytochrome P450 (CYP) involved in the metabolism of albendazole sulfoxide (ASOX) to albendazole sulfone (ASON) in patients with neurocysticercosis using antipyrine as a multifunctional marker drug. The study was conducted on 11 patients with neurocysticercosis treated with a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h). On the 5th day of albendazole treatment, 500 mg antipyrine was administered po. Blood and urine samples were collected up to 72 h after antipyrine administration. Plasma concentrations of (+)-ASOX, (-)-ASOX and ASON were determined by HPLC using a chiral phase column and detection by fluorescence. The apparent clearance (CL/f) of ASON and of the (+) and (-)-ASOX enantiomers were calculated and compared to total antipyrine clearance (CL T) and the clearance for the production of the three major antipyrine metabolites (CLm). A correlation (P<=0.05) was obtained only between the CL T of antipyrine and the CL/f of ASON (r = 0.67). The existence of a correlation suggests the involvement of CYP isoforms common to the metabolism of antipyrine and of ASOX to ASON. Since the CL T of antipyrine is a general measure of CYP enzymes but with a slight to moderate weight toward CYP1A2, we suggest the involvement of this enzyme in ASOX to ASON metabolism in man. The study supports the establishment of a specific marker drug of CYP1A2 in the study of the in vivo metabolism of ASOX to ASON.

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