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Enantioselective kinetic disposition of albendazole sulfoxide in patients with neurocysticercosis
Author(s) -
Marques Maria Paula Da Costa,
Takayanagui Osvaldo Massaiti,
Bonato Pierina Sueli,
Santos Silvia Regina Cavani Jorge,
Lanchote Vera Lucia
Publication year - 1999
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1999)11:3<218::aid-chir8>3.0.co;2-g
Subject(s) - albendazole , chemistry , neurocysticercosis , cmax , pharmacokinetics , enantiomer , chromatography , high performance liquid chromatography , sulfone , pharmacology , stereochemistry , surgery , organic chemistry , medicine , psychiatry
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® 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 (978.6–2459.8) 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. © 1999 Wiley‐Liss, Inc.