Enantioselective kinetic disposition of albendazole sulfoxide in patients with neurocysticercosis

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). Ser ial 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 Ch iralpak(R) AD column and detection by fluorescence. The pharmacokinetic par ameters showing statistically significant differences between the (+) ASOX and (-) ASOX enantiomers are presented as respective means (95% CI) as foll ows: 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) - 17 19.2 (978.62-459.8) vs 261.4 (102.9-419.8) ng.h.ml(-1) and apparent clearan ce, Cl/fm = 5.8 (3.8-7.8) vs 54.0 (35.2-72.7) l.h(-1).kg(-1). The mean valu e of 9.2 (7.6-10.9) for the AUC((+)(0-8)-ASOX)/AUC((-)(0-8)-ASOX) ratio dem onstrated plasma accumulation of the (+) enantiomer. Sulfone formation capa city, 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.