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Maria Eugenia Costa Queiroz - One of the best experts on this subject based on the ideXlab platform.
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quantification of carbamazepine carbamazepine 10 11 epoxide phenytoin and phenobarbital in plasma samples by stir bar sorptive extraction and liquid chromatography
Journal of Pharmaceutical and Biomedical Analysis, 2008Co-Authors: Regina Helena Costa Queiroz, Carlo Bertucci, Wilson Roberto Malfara, Sonia Aparecida Carvalho Dreossi, Andrea Rodrigues Chaves, Daniel A Valerio, Maria Eugenia Costa QueirozAbstract:Abstract A sensitive and reproducible stir bar-sorptive extraction and high-performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. Important factors in the optimization of SBSE efficiency such as pH, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) assured recoveries ranging from 72 to 86%, except for phenytoin (62%). Separation was obtained using a reverse phase C 18 column with UV detection (210 nm). The mobile phase consisted of water:acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08–40.0 μg mL −1 for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125–40.0 μg mL −1 for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0 μg mL −1 ). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8% and all inter-CVs were less than 10%. Limits of quantification were 0.08 μg mL −1 for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125 μg mL −1 for phenytoin. No interference of the drugs normally associated with antiepileptic drugs was observed. Based on figures of merit results, the SBSE/HPLC-UV proved adequate for antiepileptic drugs analyses from therapeutic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method.
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simultaneous plasma lamotrigine analysis with carbamazepine carbamazepine 10 11 epoxide primidone phenytoin phenobarbital and pema by micellar electrokinetic capillary chromatography mecc
Journal of Analytical Toxicology, 2003Co-Authors: Fernando Mauro Lancas, Marlene A Sozza, Maria Eugenia Costa QueirozAbstract:The determination of lamotrigine (LTG) simultaneously with carbamazepine (CBZ), carbamazepine 10,11 epoxide (CBZ-E), primidone (PRM), phenytoin (PHT), phenobarbital (PB), and 2-phenyl-2-ethyl-malonamide (PEMA) in human plasma was developed using micellar electrokinetic capillary chromatography (MECC) with a diode-array detector. The reproducibility of both separation and quantitation with MECC analysis were appropriate for the intra- and interassay coefficients. The evaluated drugs concentration intervals of LTG, 0.5-10.0 micro g/mL; CBZ, 1.0-16.0 micro g/mL; PEMA, 1.0-20.0 micro g/mL; PB, 1.0-60.0 micro g/mL; PRM, 1.0-20.0 micro g/mL; PHT, 0.7-40.0 micro g/mL; and CBZ-E, 1.0-14.0 micro g/mL were linear with correlation coefficients higher than 0.987 and coefficients of the variation of the points of the calibration curve lower than 10%. The limit of quantitation of the investigated drugs in plasma varied from 0.5 to 1.0 micro g/mL, depending upon the drug. The MECC technique was sensitive enough to work with microsamples into the subtherapeutic, therapeutic, and toxic concentrations, as well as showed to be simple and efficient when applied to monitoring therapeutic drugs in patients treated with a combination of lamotrigine and other antiepileptic drugs such as hepatic enzyme-inducing agents.
Charles R Ashby - One of the best experts on this subject based on the ideXlab platform.
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acute effects of various gaba receptor agonists and glutamate antagonists on focal hippocampal seizures in freely moving rats elicited by low frequency stimulation
Synapse, 1998Co-Authors: Hiroshi Katsumori, Yoshio Minabe, Makiko Osawa, Charles R AshbyAbstract:In this study, we examined the acute anticonvulsant spectrum of (1) dizocilpine (0.03–3 mg/kg), CGS 19755 (1–10 mg/kg), and 7-chlorokynurenic acid (1–100 nmol) (NMDA receptor/ionophore complex antagonists); (2) muscimol (0.1–10 nmol; direct GABAA agonist); (3) YM90K (3–10 mg/kg; AMPA receptor antagonist); and (4) diazepam (2 and 5 mg/kg) and carbamazepine (5 and 20 mg/kg), two standard anticonvulsants, using the partially-kindled hippocampal model for epileptic seizures in freely moving rats. The anticonvulsant effect of these compounds were assessed by determining (1) the afterdischarge (AD), which is indicative of the severity of the seizure and related to seizure maintenance, and (2) the pulse number threshold (PNT), which is indicative of the seizure threshold or initiation. In addition, ataxia, a measure of CNS dysfunction, was assessed for each compound. Overall, our results indicated that the anticonvulsant compounds examined could be classified into three categories based on effects on the AD and PNT: (1) elevation of PNT (carbamazepine, dizocilpine, CGS 19755 and 7-chlorokyurenic acid); (2) reduction of AD (diazepam and muscimol); and (3) mixed action, i.e., increased PNT and decreased AD (YM90K). Behavioral data indicated that all compounds, except carbamazepine, produced a dose- or concentration-dependent ataxia. Overall, our results suggest that NMDA receptors play a role in seizure initiation, whereas the GABAA receptors appear to be involved in seizure maintenance and AMPA receptors may be involved in both phenomena. Synapse 28:103–109, 1998. © 1998 Wiley-Liss, Inc.
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acute effects of various gaba receptor agonists and glutamate antagonists on focal hippocampal seizures in freely moving rats elicited by low frequency stimulation
Synapse, 1998Co-Authors: Hiroshi Katsumori, Yoshio Minabe, Makiko Osawa, Charles R AshbyAbstract:In this study, we examined the acute anticonvulsant spectrum of (1) dizocilpine (0.03-3 mg/kg), CGS 19755 (1-10 mg/kg), and 7-chlorokynurenic acid (1-100 nmol) (NMDA receptor/ionophore complex antagonists); (2) muscimol (0.1-10 nmol; direct GABA(A) agonist); (3) YM90K (3-10 mg/kg; AMPA receptor antagonist); and (4) diazepam (2 and 5 mg/kg) and carbamazepine (5 and 20 mg/kg), two standard anticonvulsants, using the partially-kindled hippocampal model for epileptic seizures in freely moving rats. The anticonvulsant effect of these compounds were assessed by determining (1) the afterdischarge (AD), which is indicative of the severity of the seizure and related to seizure maintenance, and (2) the pulse number threshold (PNT), which is indicative of the seizure threshold or initiation. In addition, ataxia, a measure of CNS dysfunction, was assessed for each compound. Overall, our results indicated that the anticonvulsant compounds examined could be classified into three categories based on effects on the AD and PNT: (1) elevation of PNT (carbamazepine, dizocilpine, CGS 19755 and 7-chlorokynurenic acid); (2) reduction of AD (diazepam and muscimol); and (3) mixed action, i.e., increased PNT and decreased AD (YM90K). Behavioral data indicated that all compounds, except carbamazepine, produced a dose- or concentration-dependent ataxia. Overall, our results suggest that NMDA receptors play a role in seizure initiation, whereas the GABA(A) receptors appear to be involved in seizure maintenance and AMPA receptors may be involved in both phenomena.
Stanislaw J Czuczwar - One of the best experts on this subject based on the ideXlab platform.
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synthetic cannabinoid win 55 212 2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock induced seizures in mice
Pharmacology Biochemistry and Behavior, 2011Co-Authors: Marta Misiutakrzesinska, Magdalena Florek, Piotr Tutka, Stanislaw J CzuczwarAbstract:The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN — a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four classical antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and valproate) in the mouse maximal electroshock seizure (MES) model. The results indicate that WIN (10 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test in mice. WIN (5 mg/kg) potentiated the anticonvulsant action of carbamazepine and valproate, but not that of phenytoin or phenobarbital in the MES test in mice. However, WIN administered alone and in combination with carbamazepine, phenytoin, phenobarbital and valproate significantly reduced muscular strength in mice in the grip-strength test. In the passive avoidance task, WIN in combination with phenobarbital, phenytoin and valproate significantly impaired long-term memory in mice. In the chimney test, only the combinations of WIN with phenobarbital and valproate significantly impaired motor coordination in mice. In conclusion, WIN enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test. However, the utmost caution is advised when combining WIN with classical antiepileptic drugs due to impairment of motor coordination and long-term memory and/or reduction of skeletal muscular strength that might appear during combined treatment.
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effects of new antiepileptic drugs and progabide on the mitogen induced proliferative activity of mouse splenocytes
Pharmacological Reports, 2008Co-Authors: Agnieszka Bastakaim, Stanislaw J Czuczwar, Boguslawa Budziszewska, Monika Leśkiewicz, Marta Kubera, Grzegorz Jagla, Wojciech Nowak, Wladyslaw LasonAbstract:Classical antiepileptic drugs are known to affect immune system activity, although the effects of new generation anticonvulsants on T- and B-cell-mediated immunity remain unknown. Therefore, in the present study, we compared a selection of new antiepileptic drugs with classical ones in terms of their effects on the proliferative activity of lymphocytes stimulated by concanavalin A (Con A) and lipopolysaccharide (LPS). Felbamate (3 × 10 –6 –1 0 –4 M) was the most potent in inhibiting [ 3 H]-thymidine incorporation in C57BL/6 mouse spleen cells stimulated by Con A and LPS. Treatment of the cells with stiripentol (3 × 10 –5 and 10 –4 M) and loreclezole (10 –4 M) suppressed the proliferative activity of splenocytes both after Con A and LPS stimulation. Tiagabine (3 × 10 –5 M and 10 –4 M) inhibited the Con A-induced cell proliferation, whereas the effect of LPS was attenuated only by the highest concentration of this drug (10 –4 M). Progabide showed immunosuppressive effects at concentrations o f3×1 0 –5 and 10 –4 M or only 10 –4 M after LPS or Con A stimulation, respectively. No effect on the immune parameters was observed after lamotrigine treatment. On the other hand, the Con A-induced proliferation of splenocytes was enhanced by carbamazepine (10 –5 –1 0 –4 M) and sodium valproate (5 × 10 –4 –3×1 0 –3 M). Neither carbamazepine nor sodium valproate affected the LPS-induced proliferation. These data indicate that some new antiepileptic drugs, especially felbamate at pharmacological concentrations, may suppress the mitogen-stimulated proliferative activity of mouse splenocytes. In contrast, two classical anticonvulsants (carbamazepine and sodium valproate) stimulated T-cell-mediated immunity. The above differences in the effects of particular antiepileptic drugs on the immune response may play roles in both their therapeutic efficiency and undesired effects.
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effect of amlodipine upon the protective activity of antiepileptic drugs against maximal electroshock induced seizures in mice
Pharmacological Research, 1999Co-Authors: Rafal M Kaminski, M Jasinski, E Jagiellowojtowicz, Z Kleinrok, Stanislaw J CzuczwarAbstract:Abstract Amlodipine, a calcium channel antagonist of the dihydropyridine class, up to 10 mg kg −1 (i.p.) did not significantly affect the threshold for electroconvulsions. However, this calcium channel antagonist (10 mg kg −1 ) enhanced the anticonvulsive activity of carbamazepine, valproate and phenobarbital against maximal electroshock-induced seizures in mice. Furthermore, amlodipine (5 mg kg −1 ) intensified the protection offered by carbamazepine. This effect was associated with the increased free plasma level of carbamazepine in the presence of amlodipine. Amlodipine did not influence the free or total plasma level of phenobarbital and valproate, so a pharmacokinetic interaction is not probable for valproate and phenobarbital. The anticonvulsive action and free plasma level of diphenylhydantoin was not modified by amlodipine. The combined treatment of the calcium channel antagonist and antiepileptics caused motor impairment (evaluated in the chimney test). Long-term memory (assessed in the passive avoidance test) in case of combinations of amlodipine with carbamazepine or diphenylhydantoin was not affected. The combination of amlodipine with valproate or phenobarbital significantly influenced the retention in this test. A possible usefulness of amlodipine as add-on therapy in epileptic patients may be limited by its considerable adverse effect revealed by behavioural tests. The pharmacokinetic interaction between carbamazepine and amlodipine might have some clinical importance for patients treated with these drugs.
Hiroshi Katsumori - One of the best experts on this subject based on the ideXlab platform.
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acute effects of various gaba receptor agonists and glutamate antagonists on focal hippocampal seizures in freely moving rats elicited by low frequency stimulation
Synapse, 1998Co-Authors: Hiroshi Katsumori, Yoshio Minabe, Makiko Osawa, Charles R AshbyAbstract:In this study, we examined the acute anticonvulsant spectrum of (1) dizocilpine (0.03–3 mg/kg), CGS 19755 (1–10 mg/kg), and 7-chlorokynurenic acid (1–100 nmol) (NMDA receptor/ionophore complex antagonists); (2) muscimol (0.1–10 nmol; direct GABAA agonist); (3) YM90K (3–10 mg/kg; AMPA receptor antagonist); and (4) diazepam (2 and 5 mg/kg) and carbamazepine (5 and 20 mg/kg), two standard anticonvulsants, using the partially-kindled hippocampal model for epileptic seizures in freely moving rats. The anticonvulsant effect of these compounds were assessed by determining (1) the afterdischarge (AD), which is indicative of the severity of the seizure and related to seizure maintenance, and (2) the pulse number threshold (PNT), which is indicative of the seizure threshold or initiation. In addition, ataxia, a measure of CNS dysfunction, was assessed for each compound. Overall, our results indicated that the anticonvulsant compounds examined could be classified into three categories based on effects on the AD and PNT: (1) elevation of PNT (carbamazepine, dizocilpine, CGS 19755 and 7-chlorokyurenic acid); (2) reduction of AD (diazepam and muscimol); and (3) mixed action, i.e., increased PNT and decreased AD (YM90K). Behavioral data indicated that all compounds, except carbamazepine, produced a dose- or concentration-dependent ataxia. Overall, our results suggest that NMDA receptors play a role in seizure initiation, whereas the GABAA receptors appear to be involved in seizure maintenance and AMPA receptors may be involved in both phenomena. Synapse 28:103–109, 1998. © 1998 Wiley-Liss, Inc.
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acute effects of various gaba receptor agonists and glutamate antagonists on focal hippocampal seizures in freely moving rats elicited by low frequency stimulation
Synapse, 1998Co-Authors: Hiroshi Katsumori, Yoshio Minabe, Makiko Osawa, Charles R AshbyAbstract:In this study, we examined the acute anticonvulsant spectrum of (1) dizocilpine (0.03-3 mg/kg), CGS 19755 (1-10 mg/kg), and 7-chlorokynurenic acid (1-100 nmol) (NMDA receptor/ionophore complex antagonists); (2) muscimol (0.1-10 nmol; direct GABA(A) agonist); (3) YM90K (3-10 mg/kg; AMPA receptor antagonist); and (4) diazepam (2 and 5 mg/kg) and carbamazepine (5 and 20 mg/kg), two standard anticonvulsants, using the partially-kindled hippocampal model for epileptic seizures in freely moving rats. The anticonvulsant effect of these compounds were assessed by determining (1) the afterdischarge (AD), which is indicative of the severity of the seizure and related to seizure maintenance, and (2) the pulse number threshold (PNT), which is indicative of the seizure threshold or initiation. In addition, ataxia, a measure of CNS dysfunction, was assessed for each compound. Overall, our results indicated that the anticonvulsant compounds examined could be classified into three categories based on effects on the AD and PNT: (1) elevation of PNT (carbamazepine, dizocilpine, CGS 19755 and 7-chlorokynurenic acid); (2) reduction of AD (diazepam and muscimol); and (3) mixed action, i.e., increased PNT and decreased AD (YM90K). Behavioral data indicated that all compounds, except carbamazepine, produced a dose- or concentration-dependent ataxia. Overall, our results suggest that NMDA receptors play a role in seizure initiation, whereas the GABA(A) receptors appear to be involved in seizure maintenance and AMPA receptors may be involved in both phenomena.
Gilberto Alves - One of the best experts on this subject based on the ideXlab platform.
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first hplc uv method for rapid and simultaneous quantification of phenobarbital primidone phenytoin carbamazepine carbamazepine 10 11 epoxide 10 11 trans dihydroxy 10 11 dihydrocarbamazepine lamotrigine oxcarbazepine and licarbazepine in human plasma
Analytical Abstracts, 2013Co-Authors: Ana Serralheiro, Gilberto Alves, Ana Fortuna, Marilia Rocha, Amilcar FalcaoAbstract:A sensitive and fast high-performance liquid chromatographic method coupled with ultraviolet detection is herein reported for the simultaneous determination of human plasma concentration of six antiepileptic drugs frequently used in clinical practice (phenobarbital (PB), primidone (PRM), phenytoin (PHT), carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC)) and some of their main metabolites, carbamazepine-10,11-epoxide (CBZ-E), 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (trans-diol) and licarbazepine (Lic). Sample preparation consisted of a deproteinization step with methanol followed by a solid-phase extraction procedure. Chromatographic separation was achieved in approximately 15 min on a reversed-phase C18 column using a mobile phase composed by water-methanol-acetonitrile-triethylamine (68.7:25:6:0.3, v/v/v/v; pH 6.5) pumped isocratically at 1.0 mL/min. The detector was set at 237 nm. Calibration curves were linear with regression coefficients greater than 0.992 over the concentration ranges 0.25-100 µg/mL for PB, 0.4-50 µg/mL for PRM, 0.5-50 µg/mL for PHT, 0.1-50 µg/mL for CBZ, LTG and CBZ-E, 0.1-25 µg/mL for OXC, 0.25-10 µg/mL for trans-diol and 0.15-80 µg/mL for Lic. Inter- and intra-day imprecision did not exceed 12.15% and inaccuracy was within ±14.91%. Absolute mean recoveries ranged from 78.49 to 101.04% and no interferences were observed at the retention times of the analytes and internal standard (ketoprofen). This bioanalytical method was successfully applied to real plasma samples from epileptic patients and it seems to be a suitable tool for routine therapeutic drug monitoring and also to support other clinical pharmacokinetic-based studies.
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development and validation of an hplc uv method for the simultaneous quantification of carbamazepine oxcarbazepine eslicarbazepine acetate and their main metabolites in human plasma
Analytical and Bioanalytical Chemistry, 2010Co-Authors: Ana Fortuna, Amilcar Falcao, Joana Sousa, Gilberto Alves, Patricio SoaresdasilvaAbstract:For the first time, a simple, selective and accurate high-performance liquid chromatography method with ultraviolet detection was developed and validated to quantify simultaneously three structurally related antiepileptic drugs; carbamazepine, oxcarbazepine, and the recently launched eslicarbazepine acetate and their main metabolites, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine, and licarbazepine. The method involves a solid-phase extraction and a reverse-phase C18 column with 5 cm length. The mobile phase consisting of water, methanol, and acetonitrile in the ratio 64:30:6 was selected as the best one and pumped at 1 mL/min at 40 °C. The use of this recent column and an aqueous mobile phase instead of buffers gives several advantages over the method herein developed; namely the fact that the chromatographic analysis takes only 9 min. The method was validated according to the guidelines of the Food and Drug Administration, showing to be accurate (bias within ±12%), precise (coefficient variation 0.997) over the concentration range of 0.05–30 μg/mL for carbamazepine; 0.05–20 μg/mL for oxcarbazepine; 0.15–4 μg/mL for eslicarbazepine acetate; 0.1–30 μg/mL for carbamazepine-10,11-epoxide; 0.1–10 μg/mL for 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine, and 0.1–60 μg/mL for licarbazepine. It was also shown that this method can adequately be used for the therapeutic drug monitoring of the considered antiepileptic drugs, carbamazepine, oxcarbazepine, eslicarazepine acetate, and their metabolites.