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)

Antiepileptic TDM pattern at a tertiary care hospital in India.

Therapeutic drug monitoring, a comparatively new investigational procedure in clinical pharmacology, is considered very beneficial to epilepsy patients though it increase the health care cost. Aim of this study was to determine the pattern of use of antiepileptic drug level monitoring over the last 7 years in our tertiary care centre and to critically comment on its utility. Retrospective data audit of archived data from 1998 to 2004 and age, sex, estimated levels of phenytoin, carbamazepine and phenobarbitone by HPLC were noted down, tabulated and compared. Chi square test was used for analysis. Three thousand five jundred thirty four blood samples of patients requesting for 4213 estimations of phenytoin, phenobarbitone or carbamazepine were received. Among the obtained samples, 44.0% (1058) were of children, 68.0% (2402) were of males, 0.6% (22) patients were getting 3 and 18.0% (635) getting 2, antiepileptic medications. 13.0% (546) samples showed level in the toxic range and 39.0% (1653) in lower range. There was increasing demand observed for estimation of antiepileptic drugs, over the 7 years. The number of abnormal values of phenytoin, phenobarbitone and carbamazepine did not show any significant difference over the years. The pattern was similar to that observed in other countries.

Qualitative and quantitative analysis of morphone and phenobarbitone in dried human blood stains

This study was conducted to evaluate the relationship between the age of the dried human bloodstains and the degree of detectability of morphine and phenobarbitone present in bloodstains. Detection of the drugs was studied in bloodstains at different time intervals [1, 14 days 1, 2, 3, 4, 5 months] by using thin layer chromatography [TLC] and enzyme multiplied immunoassay [EMIT]. Furthermore, the effect of storage temperature [25C and 20C] on detectability of these drugs was investigated. The results showed that both phenobarbitone and morphine could be detected by TLC from recent and old blood stains up to 5 months at both 25C by using EMIT, the percentages of both phenobarbitone and morphine concentrations were 48.39% and 82.59%, respectively, after 5 months of storage at room temperature [25C]. Thus, the decrease in morphine concentrations was less marked than that of phenobarbitone indicating that morphine was more stable in bloodstains. On the other hand, storage of blood stain samples at-20C showed slight insignificant variation in the concentrations of both phenobarbitone and morphine at all the time intervals up to 5 months. It became 98.98% and 98.80%, respectively, after 5 months. Thus, storage of bloodstains at 20C had a stability effect on the tested drugs. Statistical regression equation was used to predict the concentrations and percentages of both phenobarbitone and morphine in the dried bloodstains provided that the age of bloodstain is known at the time of assay

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.

Rapid analysis of some drugs of abuse in human blood by using EMIT and TLC techniques

A recent method for direct and rapid extraction of some drugs of abuse inwhole human blood was evaluated. Methanolic extraction of 2ml blood with 4mlmethanol yielded 0.3-3.5 ml clear extract after vigorous vortexing for 30seconds followed by centrifugation at 3000 rpm for 3 minutes. Analysis ofblood samples were done by using 2 techniques; Enzyme Multiplied Immunoassay[EMIT] and Thin Layer Chromatography [TLC] for the presence of morphine,amphetamine, phenobarbitone and methaqualone. The time taken from the startof the extraction procedure up to the point, at which the EMIT-apparatus wasinjected with the extract or TLC plates were spotted, was 10 minutes, i.e. rapid extraction. Values of detection of the four assayed drugs in the methanolic extract proved that this method of extraction is very sensitive and gives a potent, i.e. it can be used to detect drugs concentration ranges [subtherapeutic to therapeutic] for all assays

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

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

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 plasmic 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

Alguns efeitos adversos observados em pacientes epilépticos sujeitos a tratamento com fenobarbital ou fenobarbitar e fenitoína / Some adverse effects observed in patients epileptics in treatment with phenobarbital or phenobarbital and phenytoin

O fenobarbital e a fenitoína, reconhecidos como fármacos efetivos no tratamento da epilepsia, säo capazes de provocar efeitos adversos, algumas vezes graves, quer em funçäo da dose, quer em decorrência de concentraçäo plasmática, ou näo. Porém, em tratamento a longo prazo, pouco se sabe a respeito destes efeitos, razäo pela qual, procurou-se: estabelecer condiçöes para a verificaçäo das concentraçöes do fenobarbital e da fenitoína em amostras de plasma de pacientes epilépticos; verificar o comportamento bioquímico e hamtológico nas amostras de sangue destes pacientes; correlacionar níveis plasmáticos dos fármacos e efeitos adversos. Para isto, as amostras de sangue de pacientes submetidos a tratamento com fenobarbital, e com fenobarbital associado à fenitoína foram analizadas, por cromatografia em fase gasosa, para a determinaçäo dos níveis plasmáticos. Alguns parâmetros bioquímicos e hematológicos foram avaliados, os quais, na grande maioria, apresentaram-se alterados. Os resultados demonstraram que a dose, o tempo de exposiçäo e a concentraçäo plasmática influenciaram no efeito do fenobarbital e da fenitoína sobre alguns parâmetros bioquímicos e hematológicos, e que houve uma correlaçäo entre eles

Níveis plasmáticos do fenobarbital em crianças convulsivas

Verificou-se a obediência `a prescriçäo médica, através da dosagem do fenobarbital plasmático, em 70 crianças que, segundo a informaçäo dos genitores, vinham usando regularmente esse medicamento. Em apenas 32,8% dos casos, o nível sérico do fenobarbital estava nos limites terapêuticos

Niveles séricos de fenobarbital en el recién nacido con el uso de dosis diferentes calculadas para obtener un nivel predeterminado / Serum phenobarbital levels in the newborn infant with the use of different doses calculated to obtain a predetermined level

Se estudiaron 38 pacientes recién nacidos con encefalopatía hipoxicoisquémica a los cuales se les aplicaron dosis diferentes de fenobarbital calculadas para obtener niveles de 15 microg/ml (grupo I) y 25 microg/ml (grupoII). Se les determinaron niveles séricos de fenobarbital a las 12,24,48 y72 horas posteriores a la aplicación de las dosis de carga. Los niveles encontrados fueron muy cercanos a los calculados. El análisis estadístico mostró diferencia altamente significativa con p menor de 0.01 al comparar los niveles obtenidos durante el mismo momento de la toma en los grupos I y II. El análisis de varianza de los resultados obtenidos dentro del mismo grupo mostró una diferencia significativa com p menor de 0.05 entre los niveles alcanzados a las 24 y 72 horas en el grupo I, lo cual reflejó acumulación del medicamento a niveles no tóxicos. Se concluye que la utilización de fórmulas para el cálculo de dosis de carga y de mantenimiento en el recién nacido es un procedimiento útil, pero en vista de la variación individual, es necesaria la cuantificación del medicamento en forma seriada en este grupo de edad