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) 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.
|
Authors | V L Lanchote, O M Takayanagui, F H Mateus |
Journal | Chirality
(Chirality)
Vol. 16
Issue 8
Pg. 520-5
(Oct 2004)
ISSN: 0899-0042 [Print] United States |
PMID | 15290687
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Albendazole
- albendazole sulfoxide
|
Topics |
- Adult
- Albendazole
(analogs & derivatives, chemistry, metabolism, pharmacokinetics, urine)
- Female
- Humans
- Kidney
(metabolism)
- Kinetics
- Male
- Middle Aged
- Molecular Structure
- Neurocysticercosis
(blood, metabolism, urine)
- Stereoisomerism
|