Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers

This study describes the development and validation of a method for the analysis of unbound plasma concentrations of oxcarbazepine (OXC) and of the enantiomers of its active metabolite 10-hydroxycarbazepine (MHD) [S-(+)- and R-(−)-MHD] using liquid chromatography with tandem mass spectrometry (LC–MS/MS). Additionally, the free fraction of the drug is described in healthy volunteers (n = 12) after the oral administration of 300 mg OXC/12 h for 5 days. Plasma aliquots of 200 μL were submitted to ultrafiltration procedure and 50 μL of the ultrafiltrate were extracted with a mixture of tert-butyl methyl ether:dichloromethane (2:1, v/v). OXC and the MHD enantiomers were separated on a OD-H chiral phase column. The method was linear in the range of 4.0–2.0 μg/mL for OXC and of 20.0–6.0 μg/mL plasma for the MHD enantiomers. The limit of quantification was 4 ng for OXC and 20 ng for each MHD enantiomer/mL plasma. The intra- and inter-day precision and inaccuracy were less than 15%. The free fraction at the time of peak plasma concentration of OXC was 0.27 for OXC, 0.37 for S-(+)-MHD and 0.42 for R-(−)-MHD. Enantioselectivity in the free fraction of MHD was observed, with a higher proportion of R-(−)-MHD compared to S-(+)-MHD

Albendazole versus Praziquantel in the Treatment of Neurocysticercosis: A Meta-analysis of Comparative Trials

Neurocysticercosis is a parasitic disease caused by the pork tapeworm, Taenia solium, when the larval form of the parasite lodges in the central nervous system. This disease is most commonly found among members of agricultural societies with poor sanitary conditions and economies based on breeding livestock (especially pigs) with low hygiene standards. It is a disease with long history in humans, and the usual therapeutic intervention was surgery until the development of antiparasitic cysticidal agents, the most common being praziquantel and albendazole. T. solium infection can take many different forms in humans, but we concentrated on parenchymal neurocysticercosis with viable cysts. A consensus statement by a panel of experts on the subject supports the use of antiparasitic treatment, but does not indicate either albendazole or praziquantel as the drug of choice for this type of neurocysticercosis, because data from single relevant clinical trials are not conclusive. We conducted a meta-analysis to further evaluate the comparative effectiveness and safety of albendazole and praziquantel for this particular type of neurocysticercosis. The outcomes of our meta-analysis suggest that albendazole is more effective than praziquantel in controlling seizures in affected patients and in leading to the total disappearance of cysts and subsequently cure of patients with neurocysticercosis

Analysis of cerebrospinal fluid in racemose form of neurocysticercosis

The present work aimed to evaluate the pattern of CSF alterations in patients diagnosed with neurocysticercosis (NCC) in racemose form.Method This is a retrospective cohort study of patients with diagnosis of NCC in racemose form. CSF samples from 26 patients were analyzed. After patient-chart analysis was performed descriptive analysis of case studies and comparison between sexes in relation to variables were obtained with CSF by Mann-Whitney and Student’s t-tests.Results The sexes did not differ statistically when compared to pleocytosis in CSF. Eosinophils were present in 31% in samples while the ELISA test presented 80% sensitivity in this case series. Of the patient total, 24 presented a meningitis pattern with lymphocytic predominance.Conclusion There was no difference in inflammatory pattern between the sexes, with predominance of lymphocytic meningitis and 80% sensitivity by ELISA test of CSF patients with racemose form of NCC.</sec

Neurocysticercosis in Paraiba, northeast Brazil: an endemic area?

Neurocysticercosis is the central nervous system infestation by Cysticercus cellulosae, the larval form of Taenia solium. It is related to poor hygiene habits and sanitation; although Northeast is poorest Region of Brazil, it has been always stated as a non-endemic area. After the installation of computed tomography (CT) service, the incidence of neurocysticercosis began to raise in neurology services in Campina Grande PB, a city where people from the interior Paraíba can find specialized medical facilities. We analyse 5,883 CT record of the TomoHPI Computed Tomography Service from August 1993 to December 1995, observing 1.02% suggestive neurocysticercosis cases and classified them according to sex and age, precedence and socioeconomic condition. Distribution of cases according to age is homogeneous until the age of 50 (mean: 28.36 years old). Men and women are equally affected. Urban areas inhabitants represented 83.33%. Residents of Campina Grande represented 48.33% and 48.34% were residents of cities around Campina Grande (until 50 Km around) and other cities of Paraíba State. Fifty-eight patients were dependent to public health care system. We conclude that neurocysticercosis seems to be endemic in Paraíba State, demanding a more detailed study to determine its incidence/prevalence.Neurocisticercose é a infestação do sistema nervoso central pelo Cysticercus cellulosae, a forma larval da Taenia solium. É relacionada a hábitos higiênicos e sanitários precários; embora o Nordeste seja a Região mais pobre do Brasil, foi sempre considerada área não-endêmica para neurocisticercose. Depois da instalação de um serviço de tomografia computadorizada (TC), a incidência da neurocisticercose começou a crescer nos serviços de neurologia em Campina Grande PB, cidade para onde confluem pessoas de todo o interior paraibano à procura de serviços médicos especializados. Analisamos 5.883 TC realizadas no Serviço TomoHPI de Radioimagem do Hospital Pedro I de agosto de 1993 até dezembro de 1995 e 1,02% foram diagnosticadas como sugestivas de neurocisticercose e classificadas de acordo com idade e sexo, procedência e condições sócio-econômicas. A distribuição dos casos de acordo com a idade é homogênea até os 50 anos de idade (média: 28,36 anos). Homens e mulheres são afetados igualmente. Procedentes de áreas urbanas representam 83.33%. Residentes em Campina Grande representam 48.33% do total; 48,34% residem em cidades ao redor de Campina Grande (até 50 Km de distância) ou em outras cidades da Paraíba. Cincoenta e oito pacientes são dependentes do Sistema Único de Saúde. Concluimos que a neurocisticercose parece ser endêmica em nosso Estado, sendo necessários estudos mais detalhados para que tal assertiva possa ser confirmada

Population pharmacokinetics of oxcarbazepine and its metabolite 10-hydroxycarbazepine in healthy subjects

Oxcarbazepine is indicated for the treatment of partial or generalised tonic-clonic seizures. Most of the absorbed oxcarbazepine is converted into its active metabolite, 10-hydroxycarbazepine (MHD), which can exist as R-(-)- and S-(+)-MHD enantiomers. Here we describe the influence of the P-glycoprotein (P-gp) inhibitor verapamil, on the disposition of oxcarbazepine and MHD enantiomers, both of which are P-gp substrates. Healthy subjects (n=12) were randomised to oxcarbazepine or oxcarbazepine combined with verapamil at doses of 300mg b.i.d. and 80mg t.i.d., respectively. Blood samples (n=185) were collected over a period of 12h post oxcarbazepine dose. An integrated PK model was developed using nonlinear mixed effects modelling using a meta-analytical approach. The pharmacokinetics of oxcarbazepine was described by a two-compartment model with absorption transit compartments and first-order elimination. The concentration-time profiles of both MHD enantiomers were characterised by a one-compartment distribution model. Clearance estimates (95% CI) were 84.9L/h (69.5-100.3) for oxcarbazepine and 2.0L/h (1.9-2.1) for both MHD enantiomers. The volume of distribution was much larger for oxcarbazepine (131L (97-165)) as compared to R-(-)- and S-(+)-MHD (23.6L (14.4-32.8) vs. 31.7L (22.5-40.9), respectively). Co-administration of verapamil resulted in a modest increase of the apparent bioavailability of oxcarbazepine by 12% (10-28), but did not affect parent or metabolite clearances. Despite the evidence of comparable systemic levels of OXC and MHD following administration of verapamil, differences in brain exposure to both moieties cannot be excluded after P-glycoprotein inhibition