Enantioselective distribution of albendazole metabolites in cerebrospinal fluid of patients with neurocysticercosis

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Abstract
Aims Albendazole (ABZ) is effective in the treatment of neurocysticercosis. ABZ undergoes extensive metabolism to (+) and (−)‐albendazole sulphoxide (ASOX), which are further metabolized to albendazole sulphone (ASON). We have investigated the distribution of (+)‐ASOX (−)‐ASOX, and ASON in cerebrospinal fluid (CSF) of patients with neurocysticercosis.Methods Twelve patients with a diagnosis of active brain parenchymal neurocysticercosis treated with albendazole for 8 days (15 mg kg−1 day−1) were investigated. On day 8, serial blood samples were collected during the dose interval (0–12 h) and one CSF sample was taken from each patient by lumbar puncture at different time points up to 12 h after the last albendazole dose. Albendazole metabolites were determined in CSF and plasma samples by h.p.l.c. using a Chiralpak AD column and fluorescence detection. Population curves for CSF albendazole metabolite concentrationvstime were constructed.Results The mean plasma/CSF ratios were 2.6 (95% CI: 1.9, 3.3) for (+)‐ASOX and 2.7 (95% CI: 1.8, 3.7) for (−)‐ASOX, with the two‐tailedP value of 0.9873 being non‐significant. These data indicate that the transport of ASOX through the blood–brain barrier is not enantioselective, but rather depends on passive diffusion. The present results suggest the accumulation of the (+)‐ASOX metabolite in the CSF of patients with neurocysticercosis. The CSF AUC(+)/AUC(−)ratio was 3.4 for patients receiving albendazole every 12 h. The elimination half‐life of both ASOX enantiomers in CSF was 2.5 h. ASOX was the predominant metabolite in the CSF compared with ASON; the CSF AUCASOX/AUCASONratio was approximately 20 and the elimination half‐life of ASON in CSF was 2.6 h.Conclusions We have demonstrated accumulation of the (+)‐ASOX metabolite in CSF, which was about three times greater than the (−) antipode. ASOX concentrations were approximately 20 times higher than those observed for the ASON metabolite.