A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in patients with neurocysticercosis.

The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 µL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high recovery (>90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.

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

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 concentration vs time 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-tailed P 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 AUC(ASOX)/AUC(ASON) ratio 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.

Enantioselective analysis of albendazole sulfoxide in cerebrospinal fluid by capillary electrophoresis.

Albendazole (ABZ) is a benzimidazole anthelmintic drug used in the treatment of neurocysticercosis. After oral administration, ABZ is rapidly oxidized to albendazole sulfoxide (ABZSO), which has an asymmetric sulfur center, and later to albendazole sulfone (ABZSO2). ABZSO is the active metabolite responsible for the therapeutic effect of the drug. Previous studies have demonstrated pharmacokinetic differences between the two enantiomers, with the predominance of (+)-ABZSO in human biological fluids. This article describes for the first time the enantioselective analysis of ABZSO in cerebrospinal fluid (CSF) using capillary electrophoresis. The samples were prepared by liquid-liquid extraction using chloroform:isopropanol (8:2 v/v). The resolution of ABZSO enantiomers was obtained with a fused-silica capillary (60 cm x 75 microm ID) using 20 mmol/L Tris, pH 7.0, with 3.0% w/w sulfated beta-cyclodextrin as running buffer. The coefficient of variations and % relative error obtained for both within-day and between-days assays were lower than 15%. The method was linear over the concentration range of 100 to 2,500 ng/mL for each enantiomer, indicating that it is suitable for the analysis of ABZSO enantiomers in CSF from patients medicated with ABZ.

Polirradiculoneurite e neurocisticercose: relato de caso / Polyradiculoneuretis and neurocysticercosis: a case report

Relata-se o caso de doente com forma hidrocefálica e meningoencefalítica de neurocisticercose que, na primeira semana de tratamento com albendazol, desenvolveu simultaneamente polirradiculoneurite e síndrome de hipertensao intracraniana. Sao relacionados vários agentes etiológicos encontrados na literatura associados à polirradiculoneurite. Comenta-se sobre a possível fisiopatogenia desta entidade na vigência de cisticercose. Faz-se mençao a outro caso que apresentou polirradiculoneurite, do tipo síndrome de Guillain-Barré, como única manifestaçao de provável cisticercose de sistema nervoso. No caso apresentado, além da própria neurocisticercose, o stress cirúrgico e aquele relativo à gravidade do quadro clínico, um possível efeito colateral do albendazol - ou, até mesmo, uma simples coincidência - podem ser considerados como fatores relacionados à presença de polirradiculoneurite nesse doente.

Plasma and CSF levels of albendazole and praziquantel in patients with neurocysticercosis.

Albendazole or praziquantel were measured in plasma and cerebrospinal fluid (CSF) in 29 patients with neurocysticercosis. Mean levels of albendazole in plasma were 0.918 microgram/ml and in CSF were 0.392 microgram/ml and levels of praziquantel were 1.640 micrograms/ml in plasma and 0.398 microgram/ml in CSF, after doses of 15 and 50 mg/kg, respectively. Drug concentrations in CSF were 43% for albendazole and 24% for praziquantel. The drug levels obtained for both drugs showed ample individual variations that were not related to age, sex, presence of inflammation in the subarachnoid space, or therapeutic effectiveness; such variations seem to be due to individual differences in pharmacokinetics. Both drugs were effective and the doses currently used of each drug seem to be optimal for therapy of neurocysticercosis.