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

M.P Marques,O.M Takayanagui,V.L Lanchote

doi:10.1590/s0100-879x2002000200016

M.P Marques, O.M Takayanagui + Show 1 more

Open Access

https://doi.org/10.1590/s0100-879x2002000200016

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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.

Highlights

Albendazole is a drug considered to be effective for the treatment of parenchymal brain neurocysticercosis, an infestation of the central nervous system by the larval form of Taenia solium [1,2,3]
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
Since the CLT 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

Summary

Introduction

Albendazole is a drug considered to be effective for the treatment of parenchymal brain neurocysticercosis, an infestation of the central nervous system by the larval form of Taenia solium [1,2,3]. Ratios of area under the plasma concentration-time curve (AUC) of approximately 10 in patients with neurocysticercosis treated with albendazole [6,7]. Moroni et al [8] reported that in rat liver microsomes FMO favors the formation of (+)-ASOX, while CYP2C6 and/or CYP2A1 favor the production of (-)-ASOX and CYP3A leads to the formation of equivalent quantities of the (+) and (-) enantiomers. Rawden et al [5] observed that in human liver microsomes the production of ASOX depends on FMO3, CYP3A4 and CYP1A2, but mainly CYP3A4. Amri et al [9] reported the involvement of CYP in albendazole sulfonation in rats and Benoit et al [10] concluded that CYP is induced by albendazole and is responsible for the increase in ASON production using (-)-ASOX as a substrate. Autoinduction during albendazole metabolism has been reported in in vivo and in vitro studies in animals and in man [4,911]

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