Enantioselective kinetic disposition of albendazole sulfoxide in patients with neurocysticercosis

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Marques, MPD
Takayanagui, O. M.
Bonato, P. S.
Santos, SRCJ
Lanchote, V. L.
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The enantioselectivity of the kinetic disposition of albendazole sulfoxide (ASOX) was investigated in 18 patients with neurocysticercosis treated with a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h). Serial blood samples were collected on the eighth day of treatment during the last dose interval, with prorogation up to 12 h. Albendazole sulfone (ASON) and enantiomers of ASOX were analyzed in plasma samples by HPLC using a Chiralpak(R) AD column and detection by fluorescence. the pharmacokinetic parameters showing statistically significant differences between the (+) ASOX and (-) ASOX enantiomers are presented as respective means (95% CI) as follows: maximum plasma concentration, C-max = 301.6 (179.7-423.5) vs 54.9 (21.9-87.9) ng.ml(-1); elimination half-life, t(1/2) = 5.2 (4.1-6.3) vs 3.3 (2.8-3.8) h, area under the plasma concentration-time curve, AUC(ss)(0-8) - 1719.2 (978.62-459.8) vs 261.4 (102.9-419.8) ng.h.ml(-1) and apparent clearance, Cl/fm = 5.8 (3.8-7.8) vs 54.0 (35.2-72.7) l.h(-1).kg(-1). the mean value of 9.2 (7.6-10.9) for the AUC((+)(0-8)-ASOX)/AUC((-)(0-8)-ASOX) ratio demonstrated plasma accumulation of the (+) enantiomer. Sulfone formation capacity, expressed by the AUC(ss)(0-8) ratio ASON/ASOX + ASON, was 8.0 (7.0-8.9). the present data indicate enantioselectivity in the kinetic disposition of ASOX in patients with neurocysticercosis. Chirality 11:218-223, 1999. (C) 1999 Wiley-Liss, Inc.
Chirality. New York: Wiley-liss, v. 11, n. 3, p. 218-223, 1999.