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Enantioselective renal excretion of albendazole metabolites in patients with neurocysticercosis

✍ Scribed by V.L. Lanchote; O.M. Takayanagui; F.H. Mateus

Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
102 KB
Volume
16
Category
Article
ISSN
0899-0042

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✦ Synopsis

Abstract

The present study investigates the urinary excretion of the enantiomers of (+)‐ and (–)‐albendazole sulfoxide (ASOX) and albendazole sulfone (ASON) in 12 patients with neurocysticercosis treated with albendazole for 8 days (7.5 mg/kg/12 h). Serial blood samples (0–12 h) and urine (three periods of 8 h) were collected after administration of the last dose of albendazole. Plasma and urine (+)‐ASOX, (–)‐ASOX, and ASON metabolites were determined by HPLC using a chiral phase column (Chiralpak AD) with fluorescence detection. The pharmacokinetic parameters (P < 0.05) for (+)‐ASOX, (–)‐ASOX, and ASON metabolites are reported as means (95% CI); amount excreted (Ae) = 3.19 (1.53–4.85) vs. 0.72 (0.41–1.04) vs. 0.08 (0.03–0.13) mg; plasma concentration‐time area under the curve, AUC^0–24^ = 3.56 (0.93–6.18) vs. 0.60 (0.12–1.08) vs. 0.38 (0.20–0.55) μg.h/ml, and renal clearance Cl~R~ = 1.20 (0.66–1.73) vs. 2.72 (0.39–5.05) vs. 0.25 (0.13–0.37) l/h. Sulfone formation capacity, expressed as the Ae ratio ASON/ASOX + ASON, was 2.21 (1.43–2.99). These data point to enantioselectivity in the renal excretion of ASOX as a complementary mechanism to the metabolism responsible for the plasma accumulation of (+)‐ASOX. The results also suggest that the metabolite ASON is partially eliminated as a reaction product of the subsequent metabolism. Chirality 16:520–525, 2004. © 2004 Wiley‐Liss, Inc.

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