title: Albendazole metabolism in patients with neurocysticercosis: antipyrine as a multifunctional marker drug of cytochrome P450.
abstract: 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<or=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.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: M P
authors.initials: MP
authors.lastname: Marques
authors.forename: O M
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: V L
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000328:Adult; D000368:Aged; D015766:Albendazole / Q000378:metabolism* / Q000627:therapeutic use; D000871:Anthelmintics / Q000378:metabolism* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D000983:Antipyrine / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020019:Neurocysticercosis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000871:Anthelmintics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D015766:Albendazole; D000983:Antipyrine