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1.
Clin Chem Lab Med ; 58(5): 828-835, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32045349

RESUMO

Background Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) can serve as a valuable tool in optimising and individualising epilepsy treatment, especially in vulnerable groups such as pregnant women, the elderly and children. Unfortunately, TDM is often performed suboptimally due to limitations in blood collection. Therefore, we investigated volumetric absorptive micro sampling (VAMS) - a new home-sampling technique. We aimed to evaluate VAMS to determine and quantify the different AEDs and concentrations of 16 different AEDs in whole blood collected by VAMS. Methods Patient blood samples (n = 138) were collected via venepunctures at the Academic Centre for Epileptology Kempenhaeghe. AED concentrations were determined, and these concentrations were used to compare the VAMS method (whole blood) with the conventional method (serum). In addition, the recovery was examined as well as the impact of haematocrit. Finally, AED-spiked blood was used to test the stability of the AEDs inside the micro-sampler devices over a period of time and whether temperature had an effect on the stability. Results VAMS allows for an accurate detection of 16 different AEDs within 2 days after sampling. Deviation in recovery was less than 10% and high correlations were found between VAMS and conventional sampling. Moreover, haematocrit does not have an effect with values between 0.3 and 0.5 (L/L). Finally, although storage temperature of VAMS does affect some AEDs, most are unaffected. Conclusions VAMS enables an accurate detection of a wide variety of AEDs within 2 days after sampling.


Assuntos
Anticonvulsivantes/sangue , Teste em Amostras de Sangue Seco/métodos , Monitoramento de Medicamentos/métodos , Carbamazepina/sangue , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Gabapentina/sangue , Hematócrito , Humanos , Primidona/sangue , Espectrometria de Massas em Tandem , Temperatura
2.
Artigo em Inglês | MEDLINE | ID: mdl-28419925

RESUMO

Anticonvulsant drugs are often used in the treatment of epilepsy. However, their therapeutic monitoring is often necessary in order to obtain an appropriate dose adjustment, due to the proximity between their therapeutic and toxic ranges. The aim of this study was to carry out the synthesis, characterization and use of restricted access carbon nanotubes (RACNTs) in an online method for the analyses of phenobarbital and carbamazepine and primidone from untreated human blood plasma by column switching liquid chromatography. Therefore, the synthesis of RACNTs was carried out through coating commercial Carbon nanotubes with bovine serum albumin (BSA) to subsequently use them as adsorbents in a column switching system operating in the backflush mode. This material was evaluated through the construction of the kinetic and isotherm curves. The experimental data for the interaction of primidone with RACNTs were adequately adjusted to the chemisorption and Sips models for the kinetic and adsorption studies, respectively. The analytical curves ranged from 2.0 to 40.0mgL-1, with correlation coefficients higher than 0.99, for all the analytes. The LODs of 0.1, 0.1 and 0.01µgmL-1 were defined for PHB, PRM and CBZ, respectively. The relative standard deviation values ranged from 1.0% to 8.4% for the intra assay precision and from 2.7% to 7.6% for inter assay precision. The relative error values ranged from -13.4% to 7.7% for the intra assay accuracy and from -8.6% to 2.5% for the inter assay accuracy. The method was adequately used in the therapeutic monitoring of anticonvulsant drugs in human plasma samples.


Assuntos
Anticonvulsivantes/sangue , Carbamazepina/sangue , Cromatografia Líquida de Alta Pressão/instrumentação , Nanotubos de Carbono/química , Fenobarbital/sangue , Primidona/sangue , Adsorção , Animais , Anticonvulsivantes/isolamento & purificação , Carbamazepina/isolamento & purificação , Bovinos , Desenho de Equipamento , Humanos , Cinética , Limite de Detecção , Fenobarbital/isolamento & purificação , Primidona/isolamento & purificação , Proibitinas , Soroalbumina Bovina/química
3.
J Phys Chem B ; 116(14): 4370-6, 2012 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-22420638

RESUMO

Understanding the dendrimer-drug interaction is of great importance to design and optimize the dendrimer-based drug delivery system. Using atomistic molecular dynamics (MD) simulations, we have analyzed the release pattern of four ligands (two soluble drugs, namely, salicylic acid (Sal), L-alanine (Ala), and two insoluble drugs, namely, phenylbutazone (Pbz) and primidone (Prim)), which were initially encapsulated inside the ethylenediamine (EDA) cored polyamidoamine (PAMAM) dendrimer using the docking method. We have computed the potential of mean force (PMF) variation with generation 5 (G5)-PAMAM dendrimer complexed with drug molecules using umbrella sampling. From our calculated PMF values, we observe that soluble drugs (Sal and Ala) have lower energy barriers than insoluble drugs (Pbz and Prim). The order of ease of release pattern for these drugs from G5 protonated PAMAM dendrimer was found to be Ala > Sal > Prim > Pbz. In the case of insoluble drugs (Prim and Pbz), because of larger size, we observe much nonpolar contribution, and thus, their larger energy barriers can be reasoned to van der Waals contribution. From the hydrogen bonding analysis of the four PAMAM-drug complexes under study, we found intermolecular hydrogen bonding to show less significant contribution to the free energy barrier. Another interesting feature appears while calculating the PMF profile of G5NP (nonprotonated)-PAMAM-Pbz and G5NP (nonprotonated)-PAMAM-Sal complex. The PMF was found to be less when the drug is bound to nonprotonated dendrimer compared to the protonated dendrimer. Our results suggest that encapsulation of the drug molecule into the host PAMAM dendrimer should be carried out at higher pH values (near pH 10). When such complex enters the human body, the pH is around 7.4 and at that physiological pH, the dendrimer holds the drug tightly. Hence the release of drug can occur at a controlled rate into the bloodstream. Thus, our findings provide a microscopic picture of the encapsulation and controlled release of drugs in the case of dendrimer-based host-guest systems.


Assuntos
Dendrímeros/química , Preparações Farmacêuticas/sangue , Alanina/sangue , Etilenodiaminas/química , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Simulação de Dinâmica Molecular , Fenilbutazona/sangue , Fenilbutazona/química , Primidona/sangue , Primidona/química , Ácido Salicílico/sangue , Ácido Salicílico/química
4.
J Sep Sci ; 35(3): 359-66, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22258806

RESUMO

A method for the simultaneous determination of the antiepileptic drugs, phenobarbital (PHB), phenytoin (PTN), carbamazepine (CBZ), primidone (PRM) and oxcarbazepine (OXC) in human plasma and urine samples by using micro-extraction in a packed syringe as the sample preparation method connected with LC/UV (MEPS/LC/UV) is described. Micro-extraction in a packed syringe (MEPS) is a new miniaturized, solid-phase extraction technique that can be connected online to gas or liquid chromatography without any modifications. In MEPS approximately 1 mg of the solid packing material is inserted into a syringe (100-250 µL) as a plug. Sample preparation takes place on the packed bed. The bed can be coated to provide selective and suitable sampling conditions. The new method is very promising, easy to use, fully automated, inexpensive and quick. The standard curves were obtained within the concentration range 1-500 ng/mL in both plasma and urine samples. The results showed high correlation coefficients (R(2) >0.988) for all of the analytes within the calibration range. The extraction recovery was found to be between 88.56 and 99.38%. The limit of quantification was found to be between 0.132 and 1.956 ng/mL. The precision (RSD) values of quality control samples (QC) had a maximum deviation of 4.9%. A comparison of the detection limits with similar methods indicates high sensitivity of the present method. The method is applied for the analysis of these drugs in real urine and plasma samples of epileptic patients.


Assuntos
Anticonvulsivantes/sangue , Anticonvulsivantes/urina , Extração em Fase Sólida/métodos , Anticonvulsivantes/química , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Carbamazepina/química , Carbamazepina/urina , Cromatografia Líquida , Humanos , Oxcarbazepina , Fenobarbital/sangue , Fenobarbital/química , Fenobarbital/urina , Fenitoína/sangue , Fenitoína/química , Fenitoína/urina , Primidona/sangue , Primidona/química , Primidona/urina , Proibitinas , Sensibilidade e Especificidade , Extração em Fase Sólida/instrumentação , Espectrofotometria Ultravioleta
5.
Talanta ; 79(3): 669-75, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19576428

RESUMO

Application of electrospray ionization ion mobility spectrometry (ESI-IMS) as the detection technique for separation method based on molecular imprinted polymer (MIP) was investigated and evaluated. The method is exhaustively validated, including sensitivity, selectivity, recovery, reproducibility, and column capacity. The linear dynamic range of 0.02-2.00 microg mL(-1) was obtained for primidone analysis with ESI-IMS. The recovery of drug analyzed was calculated to be above 90% and the relative standard deviation (RSD), was below 3% for all experiments. Various real samples were analyzed with the coupled techniques, and the results obtained revealed the efficient clean-up of the samples using MIP separation before the analysis by ESI-IMS as a detection technique.


Assuntos
Anticonvulsivantes/análise , Anticonvulsivantes/sangue , Preparações Farmacêuticas/química , Polímeros/química , Primidona/análise , Primidona/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Anticonvulsivantes/isolamento & purificação , Calibragem , Humanos , Concentração de Íons de Hidrogênio , Impressão Molecular , Primidona/isolamento & purificação , Reprodutibilidade dos Testes , Solventes/química , Fatores de Tempo
6.
Artigo em Inglês | MEDLINE | ID: mdl-17627908

RESUMO

A rapid, simple and robust method is presented for the simultaneous determination of seven antiepileptic drugs (AEDs), including primidone, phenobarbital, phenytoin, carbamazepine with its two major metabolites carbamazepine-10,11-epoxide and carbamazepine-10,11-(trans)-dihydrodiol and the new AEDs lamotrigine, hydroxycarbazepine (active metabolite of oxcarbazepine) and zonisamide in serum by high performance liquid chromatography (HPLC)-diode array detector (DAD). After solid-phase extraction, separation is achieved on an Alltima 3C18 analytical column using isocratic elution with a mixture of acetonitrile, methanol and phosphate buffer at 45 degrees C. The method is exhaustively validated, including experimental design in combination with statistical evaluation (ANOVA) to study the robustness of chromatography and sample preparation. Commonly co-administered antiepileptic drugs do not interfere with the method. Intra-day precision (RSD<1.9%), linearity, lower limit of quantitation (LOQ<0.065 mg/l) and robustness make the method suitable for daily therapeutic drug monitoring and pharmacokinetic studies.


Assuntos
Anticonvulsivantes/sangue , Monitoramento de Medicamentos/métodos , Análise de Variância , Animais , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Bovinos , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/instrumentação , Etossuximida/sangue , Humanos , Isoxazóis/sangue , Lamotrigina , Oxcarbazepina , Fenobarbital/sangue , Fenitoína/sangue , Primidona/sangue , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida/métodos , Soluções , Manejo de Espécimes/métodos , Espectrofotometria Ultravioleta , Temperatura , Triazinas/sangue , Ácido Valproico/sangue , Zonisamida
7.
Cochrane Database Syst Rev ; (1): CD002216, 2007 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-17253477

RESUMO

BACKGROUND: The aim of drug treatment for epilepsy is to prevent seizures without causing adverse effects. To achieve this, drug dosages need to be individualised. Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients. OBJECTIVES: To review the evidence regarding the effects of therapeutic drug monitoring upon outcomes in epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialised Register (September 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 4), MEDLINE (January 1966 to April 2005) and EMBASE (1974 to May 2005). No language restrictions were imposed. We checked the reference lists of retrieved articles for additional reports of relevant studies. SELECTION CRITERIA: Randomised controlled trials comparing the outcomes of antiepileptic drug monotherapy guided by therapeutic drug monitoring with drug treatment without the aid of therapeutic drug monitoring. DATA COLLECTION AND ANALYSIS: We based this review on published aggregate data. The main outcomes measured were the proportions of patients achieving a 12-month remission from seizures, reporting adverse effects, and being withdrawn from the treatment they had been randomised to receive. MAIN RESULTS: Only one study met the inclusion criteria for the review. In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments. The antiepileptic drugs used were carbamazepine, valproate, phenytoin, phenobarbital and primidone. A 12-month remission from seizures was achieved by 60% of the patients randomised to therapeutic drug monitoring (intervention group) and by 61% in the control group. A total of 56% in the intervention group and 58% in the control group were seizure free during the last 12 months of follow up. Adverse effects were reported by 48% in the intervention group and 47% of the control group patients. Of those randomised to therapeutic drug monitoring, 62% completed the two-year follow up compared with 67% of the control group. AUTHORS' CONCLUSIONS: We found no clear evidence to support routine antiepileptic drug serum concentration measurement with the aim of reaching predefined target ranges for the optimisation of treatment of patients with newly-diagnosed epilepsy with antiepileptic drug monotherapy. However, this does not exclude the possible usefulness of therapeutic drug monitoring of specific antiepileptic drugs during polytherapy, in special situations or in selected patients, although evidence is lacking.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Anticonvulsivantes/sangue , Carbamazepina/administração & dosagem , Carbamazepina/sangue , Monitoramento de Medicamentos , Epilepsia/sangue , Humanos , Fenobarbital/administração & dosagem , Fenobarbital/sangue , Fenitoína/administração & dosagem , Fenitoína/sangue , Primidona/administração & dosagem , Primidona/sangue , Ácido Valproico/administração & dosagem , Ácido Valproico/sangue
8.
Anal Bioanal Chem ; 386(2): 256-63, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16896629

RESUMO

Simple, sensitive, and reproducible off-line solid-phase microextraction and liquid chromatography (SPME/LC) methods are described for the determination of seven anticonvulsants and tricyclic antidepressants in human plasma. Factorial design and simplex methodology were applied in the optimization of the SPME procedure for tricyclic antidepressants analyses. Important factors in the SPME efficiency are discussed, such as the fiber coatings (both lab-made and commercial), extraction time, pH, ionic strength, influence of plasma proteins, and desorption conditions. The development of the lab-made fiber coatings, namely, octadecylsilane, aminosilane, and polyurethane, are further described and applied to anticonvulsants analyses. The investigated plasmatic range for the evaluated anticonvulsants, using CW-TPR fiber, were the following: phenylethylmalonamide (3.00-40.0 microg mL(-1)), phenobarbital (5.00-40.0 microg mL(-1)), primidone (3.00-40.0 microg mL(-1)), carbamazepine and carbamazepine-epoxide (2.00-24.0 microg mL(-1)), phenytoin (2.00-40.0 microg mL(-1)), and lamotrigine (0.50-12.0 microg mL(-1)). The antidepressants' linear plasmatic concentration ranged from 75.0 to 500 ng mL(-1) for imipramine, amitriptyline, and desipramine, and from 50.0 to 500 ng mL(-1) for nortriptyline, being in all cases, the limit of quantification represented by the lowest value. The precision (interassays) for all investigated drugs in plasma sample spiked with different concentrations of each analyte and submitted to the described procedures were lower than 15%. The off-line SPME/LC methodologies developed allow anticonvulsants and antidepressants analyses from therapeutic to toxic levels for therapeutic drug monitoring.


Assuntos
Anticonvulsivantes/sangue , Antidepressivos Tricíclicos/sangue , Cromatografia Líquida/métodos , Amitriptilina/sangue , Carbamazepina/sangue , Desipramina/sangue , Compostos de Epóxi/sangue , Humanos , Concentração de Íons de Hidrogênio , Imipramina/sangue , Lamotrigina , Nortriptilina/sangue , Fenobarbital/sangue , Feniletilmalonamida/sangue , Poliuretanos/química , Primidona/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Silanos/química , Fatores de Tempo , Triazinas/sangue
9.
Yao Xue Xue Bao ; 41(3): 210-5, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16758989

RESUMO

AIM: To develop a rapid and feasible method based on micellar electrokinetic capillary chromatography (MECC) for the simultaneous determination of antiepileptic drugs (AEDs)--phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), primidone (PRM) and clonazepam (CZP) in human plasma. METHODS: Several factors that impact the separation of AEDs with MECC were investigated, such as concentration of sodium dodecyl sulfate (SDS), buffer compositions, pH, organic modifier, internal diameter and temperature, and an optimized MECC running condition was obtained the running buffer consisted of 8 mmol x L(-1) phosphate, 3 mmol x L(-1) sodium tetraborate, and 50 mmol x L(-1) sodium dodecylsulfate (SDS) (pH 8.0), containing acetonitrile (ACN) (18%) as organic modifier. Detection at 210 nm, run at 25 kV at 30 degrees C in a untreated fused silica capillary (50/45.5 cm length, 50 microm ID). RESULTS: The reproducibility of both migration time and relative peak area with MECC analysis were appropriate for the intra- and inter-assay coefficients. The evaluated drugs concentration intervals of PRM 1.0-40.0 microg x mL(-1), PB 1.0-60.0 microg x mL(-1), PHT 1.0-40.0 microg x mL(-1), CBZ 1.0-40.0 microg x mL(-1), CZP 0.2-8.0 microg x mL(-1) were linear with correlation coefficients higher than 0.999 1, and coefficients of the variation of the points of the calibration curve lower than 10%. The recoveries of AEDs varied from 80.0% to 100.0%, depending on the drug, with coefficients of the variation lower than 10.0%. CONCLUSION: The MECC technique is showed to be rapid, simple, efficient and low cost when applied to monitoring therapeutic drugs in patient treated with a combination of PHT and other AEDs such as hepatic enzyme-inducing agents.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Capilar Eletrocinética Micelar/métodos , Epilepsia/sangue , Soluções Tampão , Carbamazepina/sangue , Clonazepam/sangue , Humanos , Concentração de Íons de Hidrogênio , Fenobarbital/sangue , Fenitoína/sangue , Primidona/sangue , Sensibilidade e Especificidade , Dodecilsulfato de Sódio
10.
Biomed Chromatogr ; 18(8): 608-12, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15386509

RESUMO

A very rapid and simple MEKC method was developed for the simultaneous determination of four antiepileptic drugs, ethosuximide (Etho), primidone (Pri), phenytoin (Pht) and carbamazepine (Cbz) in human serum. Sample analysis required only 100 microL of human serum which only needed to be centrifuged, decanted and combined with the running buffer [5.3 mM Na(2)HPO(4)/3.2 mM borax buffer (pH 9.5) containing 55 mM SDS and 3.5% (v/v) acetone]. The analysis was performed in only 10 min into fused-silica capillaries (57 cm total length with 50 microm i.d. and 50 cm to the detector) using the MEKC methodology with diode-array detection at 220 nm. The calibration graphs were established for ethoximide, primidone, phenytoin and carbamazepine between 0 and 20 mg/L. Recoveries were between 85 and 87%. The simplicity of the proposed methodology makes it suitable for routine clinical use, especially for epileptic patients on polytherapy.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Capilar Eletrocinética Micelar/métodos , Soluções Tampão , Carbamazepina/sangue , Etossuximida/sangue , Humanos , Concentração de Íons de Hidrogênio , Concentração Osmolar , Fenitoína/sangue , Primidona/sangue , Controle de Qualidade , Sensibilidade e Especificidade , Dodecilsulfato de Sódio
11.
J Anal Toxicol ; 27(5): 304-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12908944

RESUMO

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.


Assuntos
Anticonvulsivantes/sangue , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Triazinas/sangue , Cromatografia Capilar Eletrocinética Micelar/métodos , Humanos , Lamotrigina , Fenobarbital/sangue , Feniletilmalonamida/sangue , Fenitoína/sangue , Primidona/sangue , Fatores de Tempo
12.
J Chromatogr Sci ; 40(4): 219-23, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12004942

RESUMO

A simple and rapid analytical method is presented for the determination of lamotrigine simultaneously with primidone, carbamazepine, carbamazepine epoxide, phenobarbital, and phenytoin in human plasma using solid-phase microextraction (SPME) and gas chromatography with thermionic specific detection. The best conditions for the SPME procedure is established as following: direct extraction on a 65-microm Carbowax-divinylbenzene fiber; 1.0 mL of a sample plasma matrix modified with 15% NaCl and 3 mL of a potassium phosphate buffer (pH 7.0); extraction temperature at 30 degrees C; and stirring at a rate of 2500 rpm for 15 min. The method shows good linearity between 0.05 and 40.0 microg/mL with regression coefficients ranging between 0.9965 and 0.9995 and a coefficient of variation of the points of the calibration curve lower than 10%. The lowest limit of quantitation for the plasma-investigated drugs varies from 0.05 to 0.20 microg/mL, according to the drug. The proposed method is sensitive enough to work into subtherapeutic and therapeutic concentrations, being that it is applied in pharmacokinetic studies and patient routine therapeutic drug monitoring.


Assuntos
Anticonvulsivantes/sangue , Carbamazepina/sangue , Cromatografia Gasosa/métodos , Fenobarbital/sangue , Fenitoína/sangue , Primidona/sangue , Triazinas/sangue , Humanos , Lamotrigina
13.
Clin Chem ; 44(5): 1085-95, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9590393

RESUMO

Discussion and development of standards for appropriate monitoring led to the following key recommendations for ordering, sampling, and analyzing antiepileptic drugs: Monitoring should usually be done on trough specimens after steady-state has been reached and always with an appropriate medical indication; non-steady-state concentrations may be indicated in selected situations. Monitoring of free phenytoin and free valproic acid is indicated in specific situations and should be done in serum. The metabolite of primidone, phenobarbital, should be measured concurrently with parent drug, but the active metabolite of carbamazepine does not need to be monitored unless the patient is exhibiting an unusual toxic response that cannot be otherwise explained. Assays used for antiepileptic drug monitoring should display a long-term CV of <10% and preferably <5%. Subtherapeutic and supratherapeutic drug concentrations should be investigated on a regular basis as part of a quality assurance process.


Assuntos
Anticonvulsivantes/sangue , Monitoramento de Medicamentos/normas , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Coleta de Amostras Sanguíneas/normas , Carbamazepina/efeitos adversos , Carbamazepina/sangue , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Interações Medicamentosas , Humanos , Fenobarbital/efeitos adversos , Fenobarbital/sangue , Fenobarbital/farmacocinética , Fenobarbital/uso terapêutico , Fenitoína/efeitos adversos , Fenitoína/sangue , Fenitoína/farmacocinética , Fenitoína/uso terapêutico , Primidona/efeitos adversos , Primidona/sangue , Primidona/farmacocinética , Primidona/uso terapêutico , Controle de Qualidade , Ácido Valproico/efeitos adversos , Ácido Valproico/sangue , Ácido Valproico/farmacocinética , Ácido Valproico/uso terapêutico
14.
Rev. cuba. pediatr ; 68(1): 26-31, ene.-abr. 1996. ilus
Artigo em Espanhol | CUMED | ID: cum-8128

RESUMO

Con el objetivo de conocer la influencia de la medicación antiepiléptica sobre los resultados escolares se estudiaron 30 niños que padecen crisis epilépticas parciales y que asisten a escuelas primarias normales. En entrevista familiar se recogió: medicación antiepiléptica usada, dosis en sangre y resultados académicos del último curso escolar que se correlacionó con las variables estudiadas con el tes de correlación múltiple. El 80 por ciento (24 niños) recibió tratamiento en monoterapia y 6 (20 por ciento) politerapia. La fenitoína correlacionó significativamente (p<0,005) con los resultados escolares M. Existe relación de los niveles elevados de droga en sangre con los peores resultados académicos (AU)


Assuntos
Epilepsias Parciais/tratamento farmacológico , Inteligência , Carbamazepina/efeitos adversos , Carbamazepina/sangue , Fenitoína/efeitos adversos , Fenitoína/sangue , Primidona/efeitos adversos , Primidona/sangue , Fenobarbital/efeitos adversos , Fenobarbital/sangue , Aprendizagem
15.
Nihon Rinsho ; 53 Su Pt 1: 928-30, 1995 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-8753590
16.
J Pharm Sci ; 83(12): 1751-3, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7891306

RESUMO

Primidone (PRM) and its active metabolites, phenylethylmalonamide (PEMA) and phenobarbital (PB), in rat plasma were simultaneously determined using a solid-phase extraction technique followed by high-performance liquid chromatography (HPLC). Twenty microliters of plasma was applied to a Bond-Elut C-18 cartridge column with 0.1 microgram of acetanilide (internal standard, IS). After the column was washed, PRM, PEMA, PB, and IS were eluted with methanol and injected into the HPLC system. Calibrations for these substances were linear in the range of 0-20 micrograms/mL. The coefficients of variation were 1.5-7.9% and 3.4-9.1% in the within-day and between-day assays, respectively. The recovery rates were 96.8-101.8%. The pharmacokinetics of these substances were examined after oral administration of PRM (50 mg/kg) to rats. The Tmax values for PRM, PEMA, and PB were 1.4, 5.7, and 6.6 h, respectively, and the Cmax values were 18.2, 8.1, and 9.6 micrograms/mL, respectively. This method is useful for pharmacokinetic studies of PRM and its active metabolites.


Assuntos
Fenobarbital/sangue , Feniletilmalonamida/sangue , Primidona/sangue , Administração Oral , Animais , Calibragem , Fenômenos Químicos , Técnicas de Química Analítica , Físico-Química , Cromatografia Líquida de Alta Pressão , Masculino , Ratos , Ratos Wistar
17.
J Pharm Biomed Anal ; 12(11): 1443-51, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7849139

RESUMO

An automated analytical method for the determination of felbamate in human plasma is described. Sample cleanup and preparation was performed by means of a Zymate II laboratory robot and consisted of a liquid-liquid extraction of felbamate and the internal standard, primidone, from human plasma to dichloromethane. The dichloromethane was evaporated and reconstituted in a phosphate buffer. Separation was performed by reversed-phase high performance liquid chromatography using a 5 microns Hypersil ODS column (150 x 4.6 mm) and a mobile phase consisting of a mixture of phosphate buffer (pH = 6.5, 0.015 M) and acetonitrile (79:21, v/v). Quantitation was performed by measurement of the UV absorbance at a wavelength of 210 nm. The lower limit of quantitation was 0.100 micrograms ml-1 using 200 microliters of plasma. The mean absolute analytical recovery of felbamate was 75.2% (n = 28). The recovery of the internal standard, primidone was 74.7% (n = 10). The within-day precision was below 3.8% at all concentration levels, except at the lower limit of quantitation (18.3%). The within-day accuracy varied between -3.7 and +7.4%. The between-day precision was below 5.0% at all concentration levels. The between-day accuracy of the method varied between -5.7 and +1.6%. The selectivity of the method towards several other anti-epileptic drugs has been demonstrated.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Líquida de Alta Pressão/métodos , Propilenoglicóis/sangue , Automação , Estabilidade de Medicamentos , Felbamato , Humanos , Fenilcarbamatos , Primidona/sangue , Reprodutibilidade dos Testes , Robótica , Sensibilidade e Especificidade
18.
Ther Drug Monit ; 16(1): 90-9, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8160262

RESUMO

An isocratic liquid-chromatographic method employing one extraction step has been developed for the quantitation of five drugs and three metabolites in human plasma. The method uses 0.100-ml aliquots of human plasma and two internal standards. Chromatographic conditions include a 4.6 mm x 150 mm Spherisorb ODS2, 3 microns a high-performance liquid chromatography, (HPLC) column, a phosphate buffer-acetonitrile-methanol (700:160:140) mobile phase, and ultraviolet (UV) absorbance detection at 210 nm. Analytes and linear quantitation ranges (microgram/ml) were felbamate (FBM) 0.391-200; primidone (PRIM), 0.098-100; phenobarbital (PHENO), 0.195-100; carbamazepine (CBZ), 0.195-100; phenytoin (PHT), 0.195-200. For CBZ-transdiol (CBZ-TR) CBZ-epoxide (CBZ-EP), and the PHT metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), the range was 0.049-25.0 micrograms/ml. Ethosuximide, methsuximide, 2-methyl-2-phenyl-succinimide (methsuximide metabolite), 2-ethyl-2-phenyl malonamide (PRIM metabolite, 5-ethyl-5-(4-hydroxyphenyl)-barbituric acid (PHENO metabolite), and mephenytoin do not interfere with quantitation of the above compounds.


Assuntos
Anticonvulsivantes/sangue , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Cromatografia Líquida de Alta Pressão , Felbamato , Humanos , Fenobarbital/sangue , Fenilcarbamatos , Fenitoína/análogos & derivados , Fenitoína/sangue , Primidona/análogos & derivados , Primidona/sangue , Propilenoglicóis/sangue , Controle de Qualidade , Análise de Regressão , Espectrofotometria Ultravioleta
19.
Electrophoresis ; 15(1): 51-61, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8143681

RESUMO

Factors influencing the establishment of an analytical window in front of the solubilized proteins in micellar electrokinetic capillary chromatography (MECC) with direct serum injection (DSI) are discussed. Both drugs and endogenous low molecular mass compounds eluting within the analytical window are identified concurrently by multi-wavelength absorption detection. Variables such as the concentration of the micelle forming substance, ionic strength, applied voltage, initial sample zone length, capillary length, selected buffer additives, insufficient renewal of the buffer in the anodic buffer vial and sample matrix are shown to impact MECC of endogenous compounds and model drugs, such as antiepileptics. For two drugs eluting within the analytical window, phenobarbital and ethosuximide, serum levels determined by DSI with external calibration are shown to compare well with levels obtained after liquid-liquid extraction and internal calibration (use of an internal standard). In addition, reproducibility of both assays is excellent. The limit of employing DSI is demonstrated with the determination of the hydrophobic drug phenytoin. Using an automated, commercial instrument and naproxen as model drug, high-speed MECC separations of high reproducibility and with a throughput of 12-15 samples per h are presented.


Assuntos
Análise Química do Sangue/métodos , Cromatografia/métodos , Micelas , Anticonvulsivantes/sangue , Soluções Tampão , Ação Capilar , Etossuximida/sangue , Humanos , Cinética , Peso Molecular , Naproxeno/sangue , Concentração Osmolar , Fenobarbital/sangue , Fenitoína/sangue , Primidona/sangue
20.
Ther Drug Monit ; 15(4): 310-6, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8236367

RESUMO

The determination of antiepileptic drugs in human serum by micellar electrokinetic capillary chromatography (MECC) with direct sample injection is discussed. Nanoliter quantities of patient sera are applied to the beginning of a fused silica capillary filled with a phosphate/borate buffer (pH 9.2) containing 75 mM sodium dodecylsulfate. Upon application of an electric field along the capillary, endogenous and drug substances are transported toward the cathode and separate into distinct zones which are detected by on-column UV absorption. Phenobarbital, ethosuximide, and primidone are shown to elute in front of the solubilized proteins, thus permitting quantitation of these drugs without any sample pretreatment. For phenobarbital and ethosuximide, MECC data obtained using the external standard method and peak areas as the basis for quantitation are shown to be in excellent agreement with those of nonisotopic immunoassays and, for ethosuximide, also with those of high-performance liquid chromatography. The correlation coefficients (n = 50) are between 0.972 and 0.986. Intraday and interday reproducibility data are 2.0-4.5% and 4.5-8.0%, respectively. For primidone, insufficient samples have been available for a comprehensive comparison of MECC data with those of other analytic techniques.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Líquida de Alta Pressão/métodos , Eletroforese , Técnica de Imunoensaio Enzimático de Multiplicação , Etossuximida/sangue , Imunoensaio de Fluorescência por Polarização , Humanos , Micelas , Fenobarbital/sangue , Primidona/sangue , Controle de Qualidade
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