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Wolfgang Thormann - One of the best experts on this subject based on the ideXlab platform.

  • Monitoring of drugs and metabolites in body fluids by capillary electrophoresis with XeHg lamp-based and laser-induced fluorescence detection.
    Electrophoresis, 2020
    Co-Authors: Jitka Caslavska, Wolfgang Thormann
    Abstract:

    Commercial capillary electrophoresis instrumentation with XeHg lamp-based and laser induced fluorescence (LIF) detection is employed for analysis of urinary 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and its major metabolites, urinary metabolites of acetylsalicylic acid, urinary benzoylecgonine in an immunoassay format, and Albendazole Sulfoxide and Albendazole sulfone in plasma. For the examples studied, the data suggest that the lamp-based detector can be employed for the monitoring of pharmacological and toxicological relevant solute concentrations, and thus represents an attractive alternative to LIF detection.

  • Monitoring of drugs and metabolites in body fluids by capillary electrophoresis with XeHg lamp‐based and laser‐induced fluorescence detection
    Electrophoresis, 2004
    Co-Authors: Jitka Caslavska, Wolfgang Thormann
    Abstract:

    Commercial capillary electrophoresis instrumentation with XeHg lamp-based and laser induced fluorescence (LIF) detection is employed for analysis of urinary 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and its major metabolites, urinary metabolites of acetylsalicylic acid, urinary benzoylecgonine in an immunoassay format, and Albendazole Sulfoxide and Albendazole sulfone in plasma. For the examples studied, the data suggest that the lamp-based detector can be employed for the monitoring of pharmacological and toxicological relevant solute concentrations, and thus represents an attractive alternative to LIF detection.

  • chiral analysis of Albendazole Sulfoxide enantiomers in human plasma and saliva using capillary electrophoresis with on column absorption and fluorescence detection
    Journal of Separation Science, 2002
    Co-Authors: Francine Prost, Jitka Caslavska, Wolfgang Thormann
    Abstract:

    The capillary zone electrophoresis (CZE) analysis of Albendazole Sulfoxide (ABZSO) enantiomers, oxfenbendazole (OxBZ) enantiomers, and Albendazole sulfone in a neutral buffer containing sulfated β-cyclodextrin as chiral selector and having UV absorption and fluorescence detection is described. For analysis of ABZSO enantiomers in plasma and saliva, the first detected enantiomer of OxBZ is employed as internal standard and the analytes are extracted using dichloromethane. With 1 mL of plasma or saliva and reconstitution of the dried extract into 50 μL of five-fold diluted buffer without chiral selector, ABZSO enantiomer concentrations as low as 0.10 μg/ mL can be determined. The assay is shown to be reproducible, robust, and suitable for analysis of ABZSO enantiomers in human plasma and saliva collected from patients that are under Albendazole pharmacotherapy for the treatment of echinococcosis of the liver. Chiral analysis of extracts of 31 patient plasma samples revealed a mean (SD) enantiomeric (-)-ABZSO/(+)-ABZSO ratio of 0.31 (0.16), confirming the stereoselectivity of the Albendazole metabolism in man. The mean (SD) of the (-)-ABZSO, (+)-ABZSO, and total ABZSO concentrations were determined to be 0.48 (0.45), 1.52 (0.80), and 1.96 (1.18) μg/mL, respectively. Furthermore, data obtained for five saliva samples that were collected at the time of blood withdrawal suggest that both the concentration of the ABZSO enantiomers and the enantiomeric ABZSO ratio are smaller compared to plasma.

  • Capillary electrophoresis with (R)-(--)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine as chiral selector for separation of Albendazole Sulfoxide enantiomers and their analysis in human plasma.
    Journal of pharmaceutical and biomedical analysis, 2002
    Co-Authors: Wolfgang Thormann, Francine Prost, Andrea Procházková
    Abstract:

    The electrokinetic separation and analysis of the enantiomers of Albendazole Sulfoxide (ABZSO), a Sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug Albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-beta-cyclodextrin. With the Pirkle-type (R)-(-)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.0-9.5 and can be detected by UV absorbance at 295 nm. Having untreated fused-silica capillaries and 50 mM (R)-DNBPG, enantiomeric resolution is dependent on capillary i.d., capillary length and operational temperature. Optimized separation is obtained for pH 9.25 and the lowest temperature setting. Preliminary data indicate that the same approach could be employed for analysis of the enantiomers of oxfenbendazole, a chiral anthelmintic Sulfoxide employed in veterinary pharmacotherapy. Analysis of plasma extracts of patients under ABZ pharmacotherapy confirmed the known enantioselectivity in the sulfoxidation of ABZ with the (+)-ABZSO being the predominant enantiomer in blood. Commencing with 2 ml of plasma, enantiomers present at >1 microg/ml could be detected only, a limitation which is based upon the strong absorbance of the chiral selector. (R)-DNBPG and ABZSO are negatively charged at pH 9.0-9.5, which prevents the application of a partial filling technique. The mobility of (R)-DNBPG is significantly larger compared to that of ABZSO. A migrating plug-plug approach based upon a plug of (R)-DNBPG migrating across the sample plug in an electroosmosis free environment obtained via a dynamic coating produced by spermine is shown to provide chiral resolution but not increased sensitivity.

  • Capillary electrophoresis with (R)-(−)-N-(3,5-dinitrobenzoyl)-α-phenylglycine as chiral selector for separation of Albendazole Sulfoxide enantiomers and their analysis in human plasma
    Journal of Pharmaceutical and Biomedical Analysis, 2002
    Co-Authors: Wolfgang Thormann, Francine Prost, Andrea Procházková
    Abstract:

    Abstract The electrokinetic separation and analysis of the enantiomers of Albendazole Sulfoxide (ABZSO), a Sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug Albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-β-cyclodextrin. With the Pirkle-type (R)-(−)-N-(3,5-dinitrobenzoyl)-α-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.0–9.5 and can be detected by UV absorbance at 295 nm. Having untreated fused-silica capillaries and 50 mM (R)-DNBPG, enantiomeric resolution is dependent on capillary i.d., capillary length and operational temperature. Optimized separation is obtained for pH 9.25 and the lowest temperature setting. Preliminary data indicate that the same approach could be employed for analysis of the enantiomers of oxfenbendazole, a chiral anthelmintic Sulfoxide employed in veterinary pharmacotherapy. Analysis of plasma extracts of patients under ABZ pharmacotherapy confirmed the known enantioselectivity in the sulfoxidation of ABZ with the (+)-ABZSO being the predominant enantiomer in blood. Commencing with 2 ml of plasma, enantiomers present at >1 μg/ml could be detected only, a limitation which is based upon the strong absorbance of the chiral selector. (R)-DNBPG and ABZSO are negatively charged at pH 9.0–9.5, which prevents the application of a partial filling technique. The mobility of (R)-DNBPG is significantly larger compared to that of ABZSO. A migrating plug–plug approach based upon a plug of (R)-DNBPG migrating across the sample plug in an electroosmosis free environment obtained via a dynamic coating produced by spermine is shown to provide chiral resolution but not increased sensitivity.

Pierina Sueli Bonato - One of the best experts on this subject based on the ideXlab platform.

  • Albendazole Sulfoxide plasma levels and efficacy of antiparasitic treatment in patients with parenchymal neurocysticercosis
    Clinical Infectious Diseases, 2019
    Co-Authors: Gianfranco Arroyo, Vera Lucia Lanchote, Pierina Sueli Bonato, Javier A Bustos, Andres G Lescano, Isidro Gonzales, Herbert Saavedra, Silvia Rodriguez, Javier E Pretell, Osvaldo Massaiti Takayanagui
    Abstract:

    BACKGROUND: The efficacy of Albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of Albendazole Sulfoxide (ASOX), the active metabolite of Albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during Albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.

  • capillary electrophoresis and hollow fiber liquid phase microextraction for the enantioselective determination of Albendazole Sulfoxide after biotransformation of Albendazole by an endophytic fungus
    Electrophoresis, 2011
    Co-Authors: Daniel Blascke Carrao, Pierina Sueli Bonato, Keyller Bastos Borges, Thiago Barth, Monica Tallarico Pupo, Anderson Rodrigo Moraes De Oliveira
    Abstract:

    : Hollow fiber liquid-phase microextraction and CE were applied for the determination of Albendazole Sulfoxide (ASOX) enantiomers in liquid culture medium after a fungal biotransformation study. The analytes were extracted from 1 mL of liquid culture medium spiked with the internal standard (rac-hydroxychloroquine) and buffered with 0.50 mol/L phosphate buffer, pH 10. The analytes were extracted into 1-octanol impregnated in the pores of the hollow fiber, and into an acid acceptor solution inside the polypropylene hollow fiber. The electrophoretic separations were carried out in 0.05 mol/L tris(hydroxymethyl)aminomethane buffer, pH 9.3, containing 3.0% w/v sulfated-β-CD (S-β-CD) with a constant voltage of +15 kV and detection at 220 nm. The method was linear over the concentration range of 250-5000 ng/mL for each ASOX enantiomer. Within-day and between-day assay precision and accuracy for the analytes were studied at three concentration levels and the values of RSD% and relative error % were lower than 15%. The developed method was applied for the determination of ASOX after a biotransformation study employing the endophytic fungus Penicillium crustosum (VR4). This study showed that the endophytic fungus was able to metabolize the Albendazole to ASOX enantioselectively. In addition, it was demonstrated that hollow fiber liquid-phase microextraction coupled to CE can be an excellent and environmentally friendly technique for the analysis of samples obtained in biotransformation studies.

  • Pharmacokinetics of combined treatment with praziquantel and Albendazole in neurocysticercosis.
    British Journal of Clinical Pharmacology, 2011
    Co-Authors: Hector H Garcia, Osvaldo Massaiti Takayanagui, Vera Lucia Lanchote, Pierina Sueli Bonato, Javier A Bustos, Andres G Lescano, Isidro Gonzales, E. Javier Pretell, John Horton, Herbert Saavedra
    Abstract:

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The antiparasitic drugs Albendazole and prazoquantel have been used together before for geohelminths, echinococcosis and cysticercosis, but there is only scarce and discrepant data on the pharmacokinetics of these drugs when given together. WHAT THIS STUDY ADDS • This is a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of Albendazole and praziquantel in 32 patients with neurocysticercosis which demonstrates that combined Albendazole + praziquantel is associated with increased Albendazole Sulfoxide concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole Sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased Albendazole Sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

  • Analysis of Albendazole metabolites by electrospray LC-MS/MS as a probe to elucidate electro-oxidation mechanism of Albendazole.
    Journal of Pharmaceutical and Biomedical Analysis, 2003
    Co-Authors: Renata De Lima, Pierina Sueli Bonato, Roberto Santana Da Silva
    Abstract:

    Abstract The electrochemical oxidation of Albendazole was accomplished by controlled potential electrolyses technique. The oxidation was carried out in different pH solutions and yields the same products obtained by in vivo and in vitro metabolism, i.e. Albendazole Sulfoxide and Albendazole sulfone. The identification of Albendazole oxidation products was carried out by LC–MS/MS.

  • simultaneous liquid chromatography tandem mass spectrometric determination of Albendazole Sulfoxide and Albendazole sulfone in plasma
    Journal of Chromatography B: Biomedical Sciences and Applications, 2003
    Co-Authors: Pierina Sueli Bonato, Vera Lucia Lanchote, Osvaldo Massaiti Takayanagui
    Abstract:

    This paper describes a simple, fast, sensitive and reliable method for the simultaneous determination of Albendazole Sulfoxide (ASOX) and Albendazole sulfone (ASON), the two most important metabolites of the drug Albendazole (ABZ), in plasma samples using liquid chromatography and tandem mass spectrometry. After liquid-liquid extraction with dichloromethane, the two Albendazole metabolites and the internal standard phenacetin were resolved in a CN column using the mobile phase methanol-water (4:6, v/v) acidified with 1% acetic acid. Detection by electrospray mass spectrometry was carried out in the positive ion mode. The method was linear up to 2500 and 250 ng/ml for ASOX and ASON, respectively, with mean recoveries of more than 85%. The precision and accuracy data, based on within- and between-day variations over 5 days, were lower than 15%. The quantitation limits of 0.5 and 5.0 ng/ml for ASON and ASOX are low enough for the method to be suitable for pharmacokinetic studies. Pharmacokinetic data obtained with the proposed method following oral administration of ABZ to a patient with neurocysticercosis are also reported.

Osvaldo Massaiti Takayanagui - One of the best experts on this subject based on the ideXlab platform.

  • Albendazole Sulfoxide plasma levels and efficacy of antiparasitic treatment in patients with parenchymal neurocysticercosis
    Clinical Infectious Diseases, 2019
    Co-Authors: Gianfranco Arroyo, Vera Lucia Lanchote, Pierina Sueli Bonato, Javier A Bustos, Andres G Lescano, Isidro Gonzales, Herbert Saavedra, Silvia Rodriguez, Javier E Pretell, Osvaldo Massaiti Takayanagui
    Abstract:

    BACKGROUND: The efficacy of Albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of Albendazole Sulfoxide (ASOX), the active metabolite of Albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during Albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.

  • Therapy for neurocysticercosis.
    Expert Review of Neurotherapeutics, 2014
    Co-Authors: Osvaldo Massaiti Takayanagui
    Abstract:

    Therapy for neurocysticercosis has advanced during the last 20 years with the advent of Albendazole (Zentel®) and praziquantel (Cysticide®). Albendazole is the current medication of choice for the treatment of neurocysticercosis and is recommended for symptomatic patients with multiple viable cysts in the brain parenchyma. Albendazole may also be useful in extraparenchymal cysticercosis, especially in the subarachnoid racemose form, when complete surgical resection of the cysts is usually impracticable. Currently, there is an intense debate over the value and safety of anticysticercal therapy. Causes for failure of anticysticercal therapy include high inter-individual variability in plasma concentration of Albendazole Sulfoxide and the complex interactions of several drugs with the Albendazole metabolite. Furthermore, Albendazole Sulfoxide is an enantiomeric mixture of (+)- and (−)-Albendazole Sulfoxide with accumulation of the (+)-enantiomer in the cerebrospinal fluid. However, the question over which en...

  • Pharmacokinetics of combined treatment with praziquantel and Albendazole in neurocysticercosis.
    British Journal of Clinical Pharmacology, 2011
    Co-Authors: Hector H Garcia, Osvaldo Massaiti Takayanagui, Vera Lucia Lanchote, Pierina Sueli Bonato, Javier A Bustos, Andres G Lescano, Isidro Gonzales, E. Javier Pretell, John Horton, Herbert Saavedra
    Abstract:

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The antiparasitic drugs Albendazole and prazoquantel have been used together before for geohelminths, echinococcosis and cysticercosis, but there is only scarce and discrepant data on the pharmacokinetics of these drugs when given together. WHAT THIS STUDY ADDS • This is a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of Albendazole and praziquantel in 32 patients with neurocysticercosis which demonstrates that combined Albendazole + praziquantel is associated with increased Albendazole Sulfoxide concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole Sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased Albendazole Sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

  • Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity
    British Journal of Clinical Pharmacology, 2011
    Co-Authors: Renata Monteiro Lima, Osvaldo Massaiti Takayanagui, Hector H Garcia, Maria Augusta Drago Ferreira, Teresa Maria De Jesus Ponte Carvalho, Bruno José Dumêt Fernandes, Eduardo Barbosa Coelho, Vera Lucia Lanchote
    Abstract:

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Pharmacokinetic interactions between Albendazole and praziquantel are based on plasma concentrations of the enantiomeric mixture of both drugs with contradictory data, although the antiparasitic activity arises from (−)-(R)-praziquantel and (+)-Albendazole Sulfoxide. WHAT THIS STUDY ADDS • The pharmacokinetic interaction between Albendazole and praziquantel is enantioselective. Praziquantel increased the plasma concentrations of (+)-Albendazole Sulfoxide more than those of (−)-Albendazole Sulfoxide and the administration of Albendazole did not change the kinetic disposition of (+)-(S)-praziquantel, but increased the plasma concentration of (−)-(R)-praziquantel. AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of Albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n= 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (Albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and Albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination.

  • simultaneous liquid chromatography tandem mass spectrometric determination of Albendazole Sulfoxide and Albendazole sulfone in plasma
    Journal of Chromatography B: Biomedical Sciences and Applications, 2003
    Co-Authors: Pierina Sueli Bonato, Vera Lucia Lanchote, Osvaldo Massaiti Takayanagui
    Abstract:

    This paper describes a simple, fast, sensitive and reliable method for the simultaneous determination of Albendazole Sulfoxide (ASOX) and Albendazole sulfone (ASON), the two most important metabolites of the drug Albendazole (ABZ), in plasma samples using liquid chromatography and tandem mass spectrometry. After liquid-liquid extraction with dichloromethane, the two Albendazole metabolites and the internal standard phenacetin were resolved in a CN column using the mobile phase methanol-water (4:6, v/v) acidified with 1% acetic acid. Detection by electrospray mass spectrometry was carried out in the positive ion mode. The method was linear up to 2500 and 250 ng/ml for ASOX and ASON, respectively, with mean recoveries of more than 85%. The precision and accuracy data, based on within- and between-day variations over 5 days, were lower than 15%. The quantitation limits of 0.5 and 5.0 ng/ml for ASON and ASOX are low enough for the method to be suitable for pharmacokinetic studies. Pharmacokinetic data obtained with the proposed method following oral administration of ABZ to a patient with neurocysticercosis are also reported.

Andrea Procházková - One of the best experts on this subject based on the ideXlab platform.

  • Capillary electrophoresis with (R)-(--)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine as chiral selector for separation of Albendazole Sulfoxide enantiomers and their analysis in human plasma.
    Journal of pharmaceutical and biomedical analysis, 2002
    Co-Authors: Wolfgang Thormann, Francine Prost, Andrea Procházková
    Abstract:

    The electrokinetic separation and analysis of the enantiomers of Albendazole Sulfoxide (ABZSO), a Sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug Albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-beta-cyclodextrin. With the Pirkle-type (R)-(-)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.0-9.5 and can be detected by UV absorbance at 295 nm. Having untreated fused-silica capillaries and 50 mM (R)-DNBPG, enantiomeric resolution is dependent on capillary i.d., capillary length and operational temperature. Optimized separation is obtained for pH 9.25 and the lowest temperature setting. Preliminary data indicate that the same approach could be employed for analysis of the enantiomers of oxfenbendazole, a chiral anthelmintic Sulfoxide employed in veterinary pharmacotherapy. Analysis of plasma extracts of patients under ABZ pharmacotherapy confirmed the known enantioselectivity in the sulfoxidation of ABZ with the (+)-ABZSO being the predominant enantiomer in blood. Commencing with 2 ml of plasma, enantiomers present at >1 microg/ml could be detected only, a limitation which is based upon the strong absorbance of the chiral selector. (R)-DNBPG and ABZSO are negatively charged at pH 9.0-9.5, which prevents the application of a partial filling technique. The mobility of (R)-DNBPG is significantly larger compared to that of ABZSO. A migrating plug-plug approach based upon a plug of (R)-DNBPG migrating across the sample plug in an electroosmosis free environment obtained via a dynamic coating produced by spermine is shown to provide chiral resolution but not increased sensitivity.

  • Capillary electrophoresis with (R)-(−)-N-(3,5-dinitrobenzoyl)-α-phenylglycine as chiral selector for separation of Albendazole Sulfoxide enantiomers and their analysis in human plasma
    Journal of Pharmaceutical and Biomedical Analysis, 2002
    Co-Authors: Wolfgang Thormann, Francine Prost, Andrea Procházková
    Abstract:

    Abstract The electrokinetic separation and analysis of the enantiomers of Albendazole Sulfoxide (ABZSO), a Sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug Albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-β-cyclodextrin. With the Pirkle-type (R)-(−)-N-(3,5-dinitrobenzoyl)-α-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.0–9.5 and can be detected by UV absorbance at 295 nm. Having untreated fused-silica capillaries and 50 mM (R)-DNBPG, enantiomeric resolution is dependent on capillary i.d., capillary length and operational temperature. Optimized separation is obtained for pH 9.25 and the lowest temperature setting. Preliminary data indicate that the same approach could be employed for analysis of the enantiomers of oxfenbendazole, a chiral anthelmintic Sulfoxide employed in veterinary pharmacotherapy. Analysis of plasma extracts of patients under ABZ pharmacotherapy confirmed the known enantioselectivity in the sulfoxidation of ABZ with the (+)-ABZSO being the predominant enantiomer in blood. Commencing with 2 ml of plasma, enantiomers present at >1 μg/ml could be detected only, a limitation which is based upon the strong absorbance of the chiral selector. (R)-DNBPG and ABZSO are negatively charged at pH 9.0–9.5, which prevents the application of a partial filling technique. The mobility of (R)-DNBPG is significantly larger compared to that of ABZSO. A migrating plug–plug approach based upon a plug of (R)-DNBPG migrating across the sample plug in an electroosmosis free environment obtained via a dynamic coating produced by spermine is shown to provide chiral resolution but not increased sensitivity.

  • capillary electrophoresis with r n 3 5 dinitrobenzoyl α phenylglycine as chiral selector for separation of Albendazole Sulfoxide enantiomers and their analysis in human plasma
    Journal of Pharmaceutical and Biomedical Analysis, 2002
    Co-Authors: Wolfgang Thormann, Andrea Procházková, Francine Prost
    Abstract:

    Abstract The electrokinetic separation and analysis of the enantiomers of Albendazole Sulfoxide (ABZSO), a Sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug Albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-β-cyclodextrin. With the Pirkle-type (R)-(−)-N-(3,5-dinitrobenzoyl)-α-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.0–9.5 and can be detected by UV absorbance at 295 nm. Having untreated fused-silica capillaries and 50 mM (R)-DNBPG, enantiomeric resolution is dependent on capillary i.d., capillary length and operational temperature. Optimized separation is obtained for pH 9.25 and the lowest temperature setting. Preliminary data indicate that the same approach could be employed for analysis of the enantiomers of oxfenbendazole, a chiral anthelmintic Sulfoxide employed in veterinary pharmacotherapy. Analysis of plasma extracts of patients under ABZ pharmacotherapy confirmed the known enantioselectivity in the sulfoxidation of ABZ with the (+)-ABZSO being the predominant enantiomer in blood. Commencing with 2 ml of plasma, enantiomers present at >1 μg/ml could be detected only, a limitation which is based upon the strong absorbance of the chiral selector. (R)-DNBPG and ABZSO are negatively charged at pH 9.0–9.5, which prevents the application of a partial filling technique. The mobility of (R)-DNBPG is significantly larger compared to that of ABZSO. A migrating plug–plug approach based upon a plug of (R)-DNBPG migrating across the sample plug in an electroosmosis free environment obtained via a dynamic coating produced by spermine is shown to provide chiral resolution but not increased sensitivity.

  • Therapeutic drug monitoring of Albendazole: determination of Albendazole, Albendazole Sulfoxide, and Albendazole sulfone in human plasma using nonaqueous capillary electrophoresis.
    Electrophoresis, 2000
    Co-Authors: Andrea Procházková, Malica Chouki, Regula Theurillat, Wolfgang Thormann
    Abstract:

    : A nonaqueous capillary electrophoretic method (NACE) for the fast determination of plasma levels of Albendazole (ABZ), Albendazole Sulfoxide (ABZSO), and Albendazole sulfone (ABZSO2) is described. The assay is based upon liquid/liquid extraction of these compounds using dichloromethane at pH 10.2 (recovery between 63 and 98%), followed by a NACE separation performed within 8 min employing a 0.036 M borate buffer (apparent pH 9.9) in a mixture of methanol and N-methylformamide (1:3) and on-column absorbance detection at 280 nm. Using 0.5 mL of plasma and extract reconstitution in 200 microL N-methylformamide, drug levels between 1.0-10 microM were found to provide linear calibration graphs. Intraday and interday imprecisions evaluated from peak area ratios (n = 5) were

  • therapeutic drug monitoring of Albendazole determination of Albendazole Albendazole Sulfoxide and Albendazole sulfone in human plasma using nonaqueous capillary electrophoresis
    Electrophoresis, 2000
    Co-Authors: Malica Chouki, Andrea Procházková, Regula Theurillat, Wolfgang Thormann
    Abstract:

    : A nonaqueous capillary electrophoretic method (NACE) for the fast determination of plasma levels of Albendazole (ABZ), Albendazole Sulfoxide (ABZSO), and Albendazole sulfone (ABZSO2) is described. The assay is based upon liquid/liquid extraction of these compounds using dichloromethane at pH 10.2 (recovery between 63 and 98%), followed by a NACE separation performed within 8 min employing a 0.036 M borate buffer (apparent pH 9.9) in a mixture of methanol and N-methylformamide (1:3) and on-column absorbance detection at 280 nm. Using 0.5 mL of plasma and extract reconstitution in 200 microL N-methylformamide, drug levels between 1.0-10 microM were found to provide linear calibration graphs. Intraday and interday imprecisions evaluated from peak area ratios (n = 5) were <10% and <12%, respectively. Corresponding imprecisions of detection times (n = 5) were <1% and <6%, respectively. The limit of detection (LOD) for ABZ, ABZSO and ABZSO2 was 8 x 10(-7) M. The reliability of the method developed was verified via analysis of 45 plasma samples obtained from patients treated with ABZ. Good agreement was obtained between the levels of ABZSO and those determined by routine HPLC. ABZ was found to be undetectable in all patient samples, whereas the levels of ABZSO2 were below or close to LOD.

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  • Albendazole Sulfoxide plasma levels and efficacy of antiparasitic treatment in patients with parenchymal neurocysticercosis
    Clinical Infectious Diseases, 2019
    Co-Authors: Gianfranco Arroyo, Vera Lucia Lanchote, Pierina Sueli Bonato, Javier A Bustos, Andres G Lescano, Isidro Gonzales, Herbert Saavedra, Silvia Rodriguez, Javier E Pretell, Osvaldo Massaiti Takayanagui
    Abstract:

    BACKGROUND: The efficacy of Albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of Albendazole Sulfoxide (ASOX), the active metabolite of Albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during Albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.

  • Pharmacokinetics of combined treatment with praziquantel and Albendazole in neurocysticercosis.
    British Journal of Clinical Pharmacology, 2011
    Co-Authors: Hector H Garcia, Osvaldo Massaiti Takayanagui, Vera Lucia Lanchote, Pierina Sueli Bonato, Javier A Bustos, Andres G Lescano, Isidro Gonzales, E. Javier Pretell, John Horton, Herbert Saavedra
    Abstract:

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The antiparasitic drugs Albendazole and prazoquantel have been used together before for geohelminths, echinococcosis and cysticercosis, but there is only scarce and discrepant data on the pharmacokinetics of these drugs when given together. WHAT THIS STUDY ADDS • This is a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of Albendazole and praziquantel in 32 patients with neurocysticercosis which demonstrates that combined Albendazole + praziquantel is associated with increased Albendazole Sulfoxide concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole Sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased Albendazole Sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

  • Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity
    British Journal of Clinical Pharmacology, 2011
    Co-Authors: Renata Monteiro Lima, Osvaldo Massaiti Takayanagui, Hector H Garcia, Maria Augusta Drago Ferreira, Teresa Maria De Jesus Ponte Carvalho, Bruno José Dumêt Fernandes, Eduardo Barbosa Coelho, Vera Lucia Lanchote
    Abstract:

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Pharmacokinetic interactions between Albendazole and praziquantel are based on plasma concentrations of the enantiomeric mixture of both drugs with contradictory data, although the antiparasitic activity arises from (−)-(R)-praziquantel and (+)-Albendazole Sulfoxide. WHAT THIS STUDY ADDS • The pharmacokinetic interaction between Albendazole and praziquantel is enantioselective. Praziquantel increased the plasma concentrations of (+)-Albendazole Sulfoxide more than those of (−)-Albendazole Sulfoxide and the administration of Albendazole did not change the kinetic disposition of (+)-(S)-praziquantel, but increased the plasma concentration of (−)-(R)-praziquantel. AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of Albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n= 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (Albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and Albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination.

  • simultaneous liquid chromatography tandem mass spectrometric determination of Albendazole Sulfoxide and Albendazole sulfone in plasma
    Journal of Chromatography B: Biomedical Sciences and Applications, 2003
    Co-Authors: Pierina Sueli Bonato, Vera Lucia Lanchote, Osvaldo Massaiti Takayanagui
    Abstract:

    This paper describes a simple, fast, sensitive and reliable method for the simultaneous determination of Albendazole Sulfoxide (ASOX) and Albendazole sulfone (ASON), the two most important metabolites of the drug Albendazole (ABZ), in plasma samples using liquid chromatography and tandem mass spectrometry. After liquid-liquid extraction with dichloromethane, the two Albendazole metabolites and the internal standard phenacetin were resolved in a CN column using the mobile phase methanol-water (4:6, v/v) acidified with 1% acetic acid. Detection by electrospray mass spectrometry was carried out in the positive ion mode. The method was linear up to 2500 and 250 ng/ml for ASOX and ASON, respectively, with mean recoveries of more than 85%. The precision and accuracy data, based on within- and between-day variations over 5 days, were lower than 15%. The quantitation limits of 0.5 and 5.0 ng/ml for ASON and ASOX are low enough for the method to be suitable for pharmacokinetic studies. Pharmacokinetic data obtained with the proposed method following oral administration of ABZ to a patient with neurocysticercosis are also reported.

  • enantioselective analysis of Albendazole Sulfoxide in cerebrospinal fluid by capillary electrophoresis
    Electrophoresis, 2001
    Co-Authors: Fernanda Orsi Paias, Osvaldo Massaiti Takayanagui, Vera Lucia Lanchote, Pierina Sueli Bonato
    Abstract:

    : 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.