Development and validation of a method for phenobarbital in serum: anticonvulsant pharmacotherapy monitoring

The therapeutic drug monitoring (TDM) is an important strategy for the effectiveness and safety of long-term pharmacotherapy, such as the use of phenobarbital as an anticonvulsant drug in epilepsy. In this sense, HLPC has been presented as a technique for the measurement of phenobarbital in serum. However, the ideal conditions for carrying out the method must be established for each laboratory reality. An analytical method using HPLC was developed and validated in order to identify and quantify Phenobarbital in blood. The chromatographic conditions were C-18 column (Shimpack XR-ODS 50L x 3.0), acetonitrile-water mobile phase (30:70, v v-1), 0.2 mL min-1 flow and reading wavelength of 210 nm. Linearity was established in the range of 2.5 to 80 µg mL-1, the linear correlation coefficient was 0.9981. The average of the coefficient of variation of the precision was 5.30%. The relative standard error of the accuracy was -2.17% and of the recovery coefficient was 97.83%. In all eleven patients, phenobarbital concentrations were below the therapeutic range. The tested method was selective, linear, precise, accurate and showed good recovery.(AU)

Laboratory evaluation and serum level of phenobarbital administered by different pathways in dogs / Avaliação laboratorial e nível sérico do fenobarbital administrado por diferentes vias em cão

Background: Anticonvulsants are widely used in the treatment of small animals for the remission of isolated seizures and recurrent seizures in epilepsy, including tonic-clonic seizures and in status epileticus. Phenobarbital is the drug of choice for the management of epileptic seizures, it is considered very effective, safe, low cost and with few side effects. Several routes of administration may be used, with the oral, intravenous and intramuscular routes being the most common, with rectal and nasal routes being the least common.Materials, Methods & Results: Twenty mongrel dogs were used in the present study (aged 1 to 6-year-old, males and females, weighing 6.0 to 17.0 kg). The patients were previously evaluated via physical examination, temperature, respiratory and heart rate, laboratory tests (erythrogram and leukogram), and serum biochemistry by analyzing the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FA), and gammaglutamyltransferase (GGT). Four experimental groups were established with five animals in each group: animals receiving intramuscular injections of phenobarbital (VIM), animals receiving nasal administration of phenobarbital (VN), animals receiving rectal administration of phenobarbital (VR), and animals receiving oral administration of phenobarbital (VO). Phenobarbital was administered every 12 h for 15 days. To determine the serum level of phenobarbital, 5 mL of jugular vein blood was collected in vacuum tubes for evaluation via hemogram. The serum level was determined after 15 days of continuous administration of phenobarbital, as stable phenobarbital serum levels can only be achieved from 10 to 15 days after the first administration. For the serum biochemistry evaluation, 10 mL of blood from the jugular vein was collected using vacuum syringes for assessing ALT, AST, GGT, and FA levels.[...](AU)

Laboratory evaluation and serum level of phenobarbital administered by different pathways in dogs / Avaliação laboratorial e nível sérico do fenobarbital administrado por diferentes vias em cão

Background: Anticonvulsants are widely used in the treatment of small animals for the remission of isolated seizures and recurrent seizures in epilepsy, including tonic-clonic seizures and in status epileticus. Phenobarbital is the drug of choice for the management of epileptic seizures, it is considered very effective, safe, low cost and with few side effects. Several routes of administration may be used, with the oral, intravenous and intramuscular routes being the most common, with rectal and nasal routes being the least common.Materials, Methods & Results: Twenty mongrel dogs were used in the present study (aged 1 to 6-year-old, males and females, weighing 6.0 to 17.0 kg). The patients were previously evaluated via physical examination, temperature, respiratory and heart rate, laboratory tests (erythrogram and leukogram), and serum biochemistry by analyzing the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FA), and gammaglutamyltransferase (GGT). Four experimental groups were established with five animals in each group: animals receiving intramuscular injections of phenobarbital (VIM), animals receiving nasal administration of phenobarbital (VN), animals receiving rectal administration of phenobarbital (VR), and animals receiving oral administration of phenobarbital (VO). Phenobarbital was administered every 12 h for 15 days. To determine the serum level of phenobarbital, 5 mL of jugular vein blood was collected in vacuum tubes for evaluation via hemogram. The serum level was determined after 15 days of continuous administration of phenobarbital, as stable phenobarbital serum levels can only be achieved from 10 to 15 days after the first administration. For the serum biochemistry evaluation, 10 mL of blood from the jugular vein was collected using vacuum syringes for assessing ALT, AST, GGT, and FA levels.[...]

Characterization and application of restricted access carbon nanotubes in online extraction of anticonvulsant drugs from plasma samples followed by liquid chromatography analysis.

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.

Quantification of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples by stir bar-sorptive extraction and liquid chromatography.

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 C18 column with UV detection (210nm). The mobile phase consisted of water:acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08-40.0microgmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125-40.0microgmL(-1) for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0microgmL(-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 0.08microgmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125microgmL(-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.

Optimization of solid-phase microextraction procedures for the determination of tricyclic antidepressants and anticonvulsants in plasma samples by liquid chromatography.

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.

Simultaneous plasma lamotrigine analysis with carbamazepine, carbamazepine 10,11 epoxide, primidone, phenytoin, phenobarbital, and PEMA by micellar electrokinetic capillary chromatography (MECC).

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.

Determination of lamotrigine simultaneously with carbamazepine, carbamazepine epoxide, phenytoin, phenobarbital, and primidone in human plasma by SPME-GC-TSD.

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.

Anti-epileptic drug intake adherence: the value of the blood drug level measurement and the clinical approach

It was evaluated the patient antiepileptic drug (AED) intake adherence in a pilot cross-sectional study carried out at a neurologic out-patient clinic of a university hospital. Ninety-three AED blood concentration (phenobarbital, phenytoin, carbamazepine) were analyzed from 24 patients. The variability of the AED blood level was measured (in the steady state period by means of the variation coefficient) and compared with the self-reported antiepileptic medication non-adherence. AED blood level according to the range (therapeutic or not), and the seizure control. It was not observed any strong correlation between the higher value of variability and the other three parameters of no adherence. The highest correlation was with the blood drug level (therapeutic or not). The evaluation of blood drug measurement alone, except in cases of extreme low adherence and variability of drug intake, is not enough for the recognition of incorrect drug intake, but the clinical markers and the self-reported adherence have to be also considered for this sort of evaluation.

Anti-epileptic drug intake adherence. The value of the blood drug level measurement and the clinical approach.

It was evaluated the patient antiepileptic drug (AED) intake adherence in a pilot cross-sectional study carried out at a neurologic out-patient clinic of a university hospital. Ninety-three AED blood concentration (phenobarbital, phenytoin, carbamazepine) were analyzed from 24 patients. The variability of the AED blood level was measured (in the steady state period by means of the variation coefficient) and compared with the self-reported antiepileptic medication non-adherence, AED blood level according to the range (therapeutic or not), and the seizure control. It was not observed any strong correlation between the higher value of variability and the other three parameters of no adherence. The highest correlation was with the blood drug level (therapeutic or not). The evaluation of blood drug measurement alone, except in cases of extreme low adherence and variability of drug intake, is not enough for the recognition of incorrect drug intake, but the clinical markers and the self-reported adherence have to be also considered for this sort of evaluation.

Influencia de la medicación antiepiléptica sobre los resultados escolares de niños epilépticos / Influence of antirpileptic drug therapy on learning outcomes of epileptic children

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)

Drogas anticonvulsivantes en suero y líquido cefalorraquideo de pacientes epilépticos: cuantificación por cromatografía líquida / Anticonvulsant drugs in serum and crebrospinal fluid of epileptical patients: liquid chromatography measurement

Se desarrolló un procedimiento de cromatografía líquida de alta presión para cuantificar simultáneamente varias drogas anticonvulsivantes en el suero y líquido cefalorraquídeo de 20 pacientes. Los coeficientes de correlación para las concentraciones en ambos líquidos decarbamazepina, fenobarbital y fenitoína fueron r=0,8588 (p<0,01), r=0,9721 (p<0,01) y r=0,9289 (p<0,01), respectivamente. Las concentraciones de cada droga en líquido cefalorraquídeo representaron porcentajes de la concentración en suero, comparables a los referidos en la literatura. Las concentraciones séricas de carbamazepina en los pacientes sin barbitúricos asociados fueron mayores que las de aquellos bajo politerapia con barbitúricos, independientemente de la dosis. La fenitoína y las concentraciones de fenobarbital en suero y líquido cefalorraquídeo. Estos resultados aqpoyan el uso de la monoterapia para tratar las epilepsias

Phenobarbital in newborns with neonatal seizures. A study of plasma levels after intravenous administration.

Phenobarbital plasma levels were studied in a group of 25 newborn infants. Phenobarbital was administered i.v. in all cases throughout the study period. The mean loading dose was 19.4 mg/kg, ranging from 16.4 to 20.5, and the mean maintenance dose was 4.0 mg/kg/day, varying from 2.6 to 5.0. We obtained mean plasma levels of 22.9 micrograms/ml, 24 h after administering the loading dose. Mean plasma levels at 4, 7, 14 and 21 days were in the therapeutic range (15-40 micrograms/ml), with only a few cases falling outside of it. There was no difference in plasma phenobarbital levels between term and pre-term infants. Side effects were not seen in infants without a severe neurological impairment prior to drug administration.

[The effect of phenobarbital on the severity of intraventricular hemorrhage]. / Efecto del fenobarbital sobre la gravedad de la hemorragia intraventricular.

During an eight-months period, we studied every newborns under 34 gestation weeks who needed mechanical ventilation (MV) from the moment they were born and whom had an ultrasonogram without intraventricular hemorrhage in the first six hours after birth. Patient were separated in two groups: the first, a group of 30 patients received phenobarbital 20 mg/kg IV in the first 6 hours of life and then 2.5 mg/kg, I.V., every 12 hours for the next five days. Blood levels were measured 24 and 96 hours after the initial dose was given. The second group of 30 patients was not treated with phenobarbital. In both groups a brain ultrasonogram was made every 48 hours until 15 days of life. There were no difference in weight, gestational age, Apgar score, way of birth, initial diagnosis, incidence of pneumothorax, mortality and days with MV between the two groups. During the first three days were measured blood glucose, blood pressure, mean airway pressure, PCO2, PO2 and found no significant difference between both groups. The blood pH showed statistically significant difference, with better values at 48-72 hours in the group treated with phenobarbital. The global incidence of intraventricular hemorrhage was 16 (53%) in the group treated and 14 (46%) in the not treated, this difference was not statistically significant. The degree of hemorrhage, found was: I and II degree, eleven (69%) in the treated group and four (28%), in the control group; III and IV degree five (31%), in the treated group and ten (71%), in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Dosagens séricas repetidas de anticonvulsivantes em pacientes epiléticas / Repetitive serum dosages of anticonvulsants in epileptic patients

Para avaliaçäo da aderência ao tratamento em epilépticas crônicas estudamos 38 pacientes através de 144 dosagens séricas repetidas de anticonbulsivantes a intervalos semanais. Todas as pacientes apresentavam crises supostamente de dificil controle, isto é, tiveram crises no mês anterior à última consulta. O nível sérico da droga antiepiléptica estava abaixo da faixa terapêutica em 34// das amostras analisadas. Houve ainda variaçöes semanais importantes do nível terapêutico para subterapêutico das drogas e vice-versa. Baseados nestes achados sugere-se que a estratégia de dosagens séricas repetidas possa diferenciar as pacientes resistentes à droga daquelas que näo fazem uso regular do medicamento

[Repetitive serum determinations of anticonvulsants in epileptic patients]. / Dosagens séricas repetidas de anticonvulsivantes em pacientes epilépticas.

To evaluate complacence in chronic epileptic women we collected weekly 144 blood samples from 38 patients for antiepileptic drugs determination. All the patients were supposed to have uncontrolled seizures using phenobarbital, phenytoin or carbamazepine monotherapeutically. We found that 34% of the blood levels were below the standard normal range. Blood level with great weekly variations were interpreted as inadequate intake by the patient. We conclude that repetitive antiepileptic blood levels determination may elucidate if the patient has drug-resistant seizures or if the patient is not complacent to the drug therapy.

Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls.

Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27 +/- 10, mean +/- sd) were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25 +/- 12 mu/ml) of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means). Patients performed worse than controls in all 6 tests (p less than 0.05 to p less than 0.001), indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.

Cognitive Functions of epileptic patients on monotherapy with phenobarbitone and healthy controls

Estudos quantitativos anteriores têm demonstrado que hereditariedade, dano cerebral, aspectos psico-sociais, fenômenos ictais e interictais e drogas antiepilépticas interferem na disfunçäo cognitiva de pacientes epilépticos. Neste estudo os métodos objetivos incluiram memória e reconhecimento imediatos e tardio nas figuras, teste de Stroop e seleçäo auditiva. Vinte pacientes com epilepsia localizada sintomática entre 17 e 52 anos de idade (27 ñ 10, média ñ d.p.) foram comparados a grupo controlado para idade e classe social. Os pacientes tinham concentraçöes terapêuticas (25 ñ 12 µg/ml) de fenobarbital e epilepsia ativa com 1,94 crises generalizadas tônico-clônicas, 0,85 parciais simples e 6,28 parciais complexas por mês (médias). Pacientes tiveram performances piores que controles em todos testes (p < 0.05 a 0.001), indicando disfunçäo cognitiva generalizada relacionada com crises epilépticas e/ou tratamento com barbitúricos. Sugerimos que outros estudos com populaçöes uniformes em regimes monoterapêuticso e síndromes epilépticas uniformes sejam realizados, para isolar fatores relacionados à disfunçäo cognitiva de apcientes epilépticos

Efeitos do fenobarbital em pacientes com nefrolitíase de cálcio / Phenobarbital effects in patients with calcium nephrolithiasis

Os autores apresentam os resultados de um estudo realizado em 20 pacientes com nefrolitíase cálcica tratados com fenobarbital, 100mg/dia, durante 32 dias. O tratamento com o fenobarbital reduziu a calcemia (9,21 ñ 0,57mg/dl vs. 8,30 ñ 1,07mg/dl; p < 0,05), a calciúria (185,4 ñ 74,91mg/24h vs. 132,8 ñ 50,12mg/24h; p < 0,001), a uricosúria (785,27mg/24h vs. 551,8 ñ 215,02mg/24h; p < 0,05) e a FEAU (12,07 ñ 5,95// vs. 8,33 ñ 3,00//; p < 0,05) e elevou a RTP (82,45 ñ 6,20// vs. 89,11 ñ 4,11//; p < 0,01). O TSCa näo sofreu alteraçöes. Visto que o fenobarbital é uma droga segura, cujos efeitos nos parâmetros hematológicos, hepáticos e renais säo despreziveis, e a ocorrência de doença óssea desmineralizante é rara, os autores consideram que o medicamento deva ser objeto de investigaçäo no tratamento da litíase cálcica, principalmente quando a hipercalciúria e/ou a hiperuricosúria estiverem associadas

Importancia de la dosificación plasmática de fármacos antiepilépticos en el tratamiento de la epilepsia: estudio de 65 pacientes / Significance of plasic dosification of antiepileptic drugs in the management of epilepsia: study of 65 cases

Se presentan los resultados del primer trabajo cubano sobre dosificación de antiepilépticos en plasma y tratamiento de la epilepsia, de carácter interdisciplinario y en colaboración por 4 instituciones. Se estudiaron 65 adultos que padecían crisis epilépticas parciales, tonicoclónicas generalizadas o ambas, con más de 1 año, por lo menos, de observación en la Consulta Especial de Epilepsia. Se utilizó la cromatografía líquida de alta resolución para la dosificación plasmática de 3 drogas: defenilhidantoína (DFH) carbamazepina (CBZ) y fenobarbital (FB). El 58,4

de los pacientes tenían un control total de sus crisis al momento de la determinación; el 32,3 un control parcial y el 9,2 no estaba controlado. La relación entre el control clínico y las cifras de antiepilépticos en plasma fue adecuada. Los pacientes no contolados tenían una concentración promedio más baja (entre 11,72 y 13,87 *g/mL) que los controlados (24,5 *g/mL para la DFH. Las cifras de DFH por debajo de 15 *g/mL se comportaron como subterapéuticas en nuestra serie. La concentración media de FB fue de 13,87 *g/mL y la de CBZ de 5,50. La DFH sola, la CBZ sola y la DFH asociada al FB fueron igualmente efectivas para el control de la crisis. Las dosis terapéuticas de DFH se encontraron en 4,8 mg por kg de peso corporal, y las de CBZ en 10,9. SE presentan casos demostrativos y se comentan los avances que han representado estas técnicas para el tratamiento de la epilepsia, por lo que se sugiere la introducción de las mismas en nuestro país al nivel provincial por la organización de salud cubana (AU)