Enantioselective renal excretion of albendazole metabolites in patients with neurocysticercosis.
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) microg x 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.
Lanchote
V L
VL
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto, Brazil. lanchote@fcfrp.usp.br
Takayanagui
O M
OM
Mateus
F H
FH
D000328:Adult; D015766:Albendazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D020019:Neurocysticercosis / Q000097:blood / Q000378:metabolism* / Q000652:urine*; D013237:Stereoisomerism
D015766:Albendazole; C027186:albendazole sulfoxide