RESUMO
La teofilina es uno de los medicamentos más antiguos utilizados para tratamiento del asma. En este artículo se resumen las indicaciones para su utilización en asma, y se concluye que las principales indicaciones son para asma crónica, particularmente nocturna, aunque se puede utilizar en crisis asmáticas agudas refractarias al manejo inicial con beta agonistas y esteroides
Assuntos
Criança , Humanos , Asma/tratamento farmacológico , Teofilina/metabolismo , Teofilina/farmacologia , Teofilina/farmacocinética , Efeito Rebote , Estado Asmático/tratamento farmacológicoRESUMO
Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses. However, there have been several case reports published recently which demonstrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously. We studied eleven elderly (mean age, 69.0 +/- 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, followed by one week intake of the same dose of theophylline plus ranitidine tablets, 150 mg every 12 h. At the end of each period, blood samples were obtained 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12 h after the morning dose for the determination of serum theophylline levels. The peak theophylline concentration (Tmax) was achieved after 4.1 +/- 0.9 h while the patients were taking theophylline, and after 2.9 +/- 1.4 h with the combined regimen. This difference was statistically significant (P < 0.01). In only 3/11 subjects did Tmax remain unchanged during both phases of the study. The mean theophylline clearance rates while the patients were receiving theophylline alone (39.58 +/- 19.89 ml/min) and when they were receiving both medications (34.42 +/- 10.55 ml/min) were similar. The mean serum levels while the patients were receiving theophylline alone were slightly higher but not statistically different. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patients with COPD who is also given ranitidine.
Assuntos
Antagonistas dos Receptores H2 da Histamina/farmacologia , Pneumopatias Obstrutivas/metabolismo , Ranitidina/farmacologia , Teofilina/farmacologia , Vasodilatadores/farmacologia , Fatores Etários , Idoso , Interações Medicamentosas , Quimioterapia Combinada , Antagonistas dos Receptores H2 da Histamina/metabolismo , Humanos , Pessoa de Meia-Idade , Ranitidina/metabolismo , Teofilina/metabolismo , Vasodilatadores/metabolismoRESUMO
Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses. However, there have been several case reports published recently which demostrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously. We studied eleven elderly (mean age, 69,0 + or - 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, followed by one week intake of the same dose of theophylline plus ranitidine tables, 150 mg every 12h. At the end of each period, blood samples were obtained 0,1,2,3,4,6,7,8 and 12h after the morning dose for the determination of serum theophylline levels. the peak theophylline concentration was achieved after 4.1 + or - 0.9 h while the patients were taking theophylline, and after 2.9 + or - 1.4 h with the combined regimen. This difference was statistically significant. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patient with COPD who is also given ranitidine.
Assuntos
Humanos , Pessoa de Meia-Idade , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Pneumopatias Obstrutivas/metabolismo , Ranitidina/administração & dosagem , Teofilina/administração & dosagem , Fatores Etários , Cromatografia Líquida de Alta Pressão , Interações Medicamentosas , Quimioterapia Combinada , Ranitidina/sangue , Ranitidina/metabolismo , Teofilina/sangue , Teofilina/metabolismoRESUMO
The seeds of Guaraná are rich in xanthines and are used for the preparation of guaraná powder which is very commonly given to horses as a 'tonic' in Brazil. In this paper, the xanthine content of guaraná powder was determined, in addition to its clearance time in horses. Thin-layer chromatography was used as a screening procedure and high-performance liquid chromatography was performed to quantify the drugs in both the powder and urine samples. The guaraná powder was found to contain 2.16, 1.10 and 36.78 mg g-1 of theobromine (TB), theophylline (TP) and caffeine (CF), respectively, and in urine it was possible to detect TB and TP up to 13 d and CF up to 9 d after the administration of guaraná powder.
Assuntos
Cafeína/administração & dosagem , Teobromina/administração & dosagem , Teofilina/administração & dosagem , Xantinas/urina , Administração Oral , Animais , Cafeína/análise , Cafeína/química , Cafeína/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina/métodos , Combinação de Medicamentos , Cavalos , Análise de Regressão , Reprodutibilidade dos Testes , Sementes , Teobromina/análise , Teobromina/química , Teobromina/metabolismo , Teofilina/análise , Teofilina/química , Teofilina/metabolismo , Xantinas/análiseRESUMO
Conflicting reports raise a question about decreased plasma clearance (Clp) of theophylline in man during viral infections. Thus a dilemma exists concerning requisite dose adjustments. We examined this issue by retrospectively evaluating theophylline Clp in children infected with respiratory syncytial virus (RSV). Two pharmacokinetic approaches were applied to a one-compartment open model to fit theophylline concentrations during 83 hospitalizations of 76 children, 6 to 48 months of age, who received intravenous theophylline therapy and were tested for RSV infection. Iterative linear regression analyses of all theophylline data were used to estimate apparent volume of distribution, elimination rate constant, plasma half-life, and Clp in 39 of the hospitalizations. When insufficient data were available to distinguish apparent volume of distribution and elimination rate constant (n = 44), steady-state estimates of Clp were calculated. An age-matched and percentile body weight-matched cohort design presented RSV as the primary covariate. Theophylline Clp was similar in 29 matched RSV-infected and -uninfected pairs (1.32 +/- 0.14 and 1.25 +/- 0.05 ml/kg per minute, respectively), as were other pharmacokinetic values. Unexpectedly, a significant, inverse linear relationship was found for Clp and percentile body weight. Additionally, children born prematurely and hospitalized in the neonatal intensive care unit had significantly higher theophylline Clp; this did not affect findings regarding RSV infection. Theophylline Clp was not decreased in RSV-infected children. Current theophylline dosing recommendations for young children infected with RSV should not be altered, but careful monitoring of plasma theophylline levels should be continued.
Assuntos
Vírus Sinciciais Respiratórios , Infecções por Respirovirus/metabolismo , Teofilina/farmacocinética , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Infecções por Respirovirus/sangue , Estudos Retrospectivos , Teofilina/sangue , Teofilina/metabolismoRESUMO
OBJECTIVES: To determine whether the method of intoxication influences the metabolic disturbances and pattern of life-threatening events that occur after theophylline intoxication in children. METHODS: Five-year prospective observational study of consecutive pediatric patients referred to a regional poison control center with a theophylline concentration (theo) greater than or equal to 30 micrograms/ml. At the time of referral, intoxication was categorized as acute (single toxic exposure), chronic (long-term toxic exposure), or acute-on-therapeutic (single toxic exposure superimposed on maintenance therapy). RESULTS: One-hundred twenty-five patients were monitored. Mean age was 12 years (range, 3 days to 20 y). Seventy-four patients (59%) had acute intoxication, 31 (25%) had chronic intoxication, and 20 (16%) had acute-on-therapeutic intoxication. Mean peak serum (theo) was 55 micrograms/ml. Life-threatening events occurred in 12 patients (10%). Patients with acute intoxication had a significantly lower serum potassium level (3.04 vs 3.80 mmol/L; p less than 0.001) and higher serum glucose level (10.8 vs 7.0 mmol/L (194 vs 127 mg/dl); p less than 0.001) than did children with chronic intoxication. Although life-threatening events (seizures or arrhythmias) occurred at a similar rate across categories, the (theo) at which these events occurred was significantly higher in patients with acute intoxication than in those with chronic intoxication (100 vs 42 micrograms/ml; p = 0.02). Among children with chronic intoxication, those who had life-threatening events had (theo) similar to those who remained well (42 vs 47 micrograms/ml) but were significantly younger (1.6 vs 8.0 years; p less than 0.001). CONCLUSIONS: These data indicate that method of intoxication has significant effects on the metabolic and clinical consequences of theophylline poisoning. Life-threatening events occur in those with acute theophylline intoxication at significantly higher (theo) than in those with chronic intoxication. After chronic intoxication, peak (theo) does not identify patients at risk for life-threatening events; young age appears to be the primary risk factor. These findings potentially complicate the management of theophylline poisoning, given the difficulty of extracorporeal drug removal in young infants.
Assuntos
Teofilina/intoxicação , Doença Aguda , Adolescente , Adulto , Fatores Etários , Arritmias Cardíacas/induzido quimicamente , Bicarbonatos/sangue , Criança , Pré-Escolar , Doença Crônica , Humanos , Hiperglicemia/induzido quimicamente , Hipopotassemia/induzido quimicamente , Lactente , Recém-Nascido , Erros de Medicação , Estudos Prospectivos , Fatores de Risco , Convulsões/induzido quimicamente , Teofilina/administração & dosagem , Teofilina/sangue , Teofilina/metabolismoRESUMO
The pharmacokinetics of theophylline were studied in 12 patients with hepatosplenic mansoniasis, 14 patients with cirrhosis and 16 normal controls. Following a single intravenous dose of aminophylline volumes of distribution, serum half-lives and body clearances were determined. Volumes of distribution of theophylline in patients with schistosomiasis (mean 0.624 l/kg) did not differ from cirrhotic patients (mean 0.616 l/kg) or normal controls (mean 0.593 l/kg). Cirrhotic patients had a prolonged half-life compared to normal subjects (mean 22.1 vs. 9.9 h), while patients with schistosomiasis did not substantially differ from normal controls (15.8 vs. 9.9 h). Body clearance in patients with schistosomiasis was similar to controls (34.02 vs. 49.20 ml/h per kg) but decreased (29.24 ml/h per kg) in patients with cirrhosis. Individual analysis of the group with schistosomiasis disclosed three patients with reduced theophylline elimination. No relationship was found between laboratory tests of liver function and the pharmacokinetics of theophylline in any group. The administration of theophylline to patients with hepatosplenic schistosomiasis, although less dangerous than in cirrhosis, must be closely followed.
Assuntos
Cirrose Hepática/metabolismo , Hepatopatias Parasitárias/metabolismo , Esquistossomose mansoni/metabolismo , Esplenopatias/metabolismo , Teofilina/metabolismo , Adolescente , Adulto , Idoso , Aminofilina/administração & dosagem , Animais , Feminino , Meia-Vida , Humanos , Injeções Intravenosas , Fígado/metabolismo , Fígado/parasitologia , Fígado/fisiologia , Hepatopatias Parasitárias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Schistosoma mansoni/isolamento & purificação , Baço/metabolismo , Baço/parasitologia , Baço/fisiologia , Esplenopatias/fisiopatologia , Teofilina/farmacocinéticaRESUMO
We evaluated pharmacokynetic parameters and bioavailability of 4 sustained release teophylline preparations. A crossover design was used in 12 healthy males aged 22 to 27 years old. each individual recived 250 mg iv followed by 250 mg orally of each preparation, and then 400mg rapid acting aminophylline. A 7 day period was allowed between drug courses. HPLC was used to determine plasma levels of teophylline at regular intervals up to 48 hr following drug administration. Significant (p < 0.05) differences in pharmacokynetic parameters were found among preparations, 2 of them having larger integrals of plasma levels and one of them different times to peak plasma level and peak plasma concentration, compared to both remaining preparations
Assuntos
Teofilina/farmacologia , Teofilina/metabolismo , Disponibilidade BiológicaRESUMO
La tofilina, una metilxantina, es un broncodilatador mayor para el tratamiento del asma bronquial. Su mecanismo de acción es desconocido. Sin embargo, se han determinado numerosas interacciones en diversos pasos metabólicos y celulares que pudieran tener relación con su efecto broncodilatador, como el antagonismo con los receptores de adenosina, su influencia en el metabolismo del calcio y su acción sobre las prostaglandinas. La terapia óptima con teofilina debe producir niveles sanguíneos de 10 a 20 ug/ml (que es su rango terapéutico), lo cual pernmite obtener el máximo efecto broncodilatador con las mínimas reacciones adversas. Las acciones farmacológicas de la teofilina sobre el sistema cardiovascular, el sistema nervioso central, el tubo digestivo, la musculatura lisa y estriada, así como sus efectos beneficiosos sobre el tracto respiratorio deben ser muy bien conocidos por el médico para que así pueda utilizar ésta droga con el mayor beneficio y con la menor cantidad posible de reacciones adversas
Assuntos
Humanos , Asma/tratamento farmacológico , Teofilina , Obstrução das Vias Respiratórias/tratamento farmacológico , Teofilina/efeitos adversos , Teofilina/metabolismo , Teofilina/farmacologia , Teofilina/uso terapêuticoAssuntos
Humanos , Feminino , Masculino , Broncodilatadores/classificação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Cromolina Sódica/administração & dosagem , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/uso terapêutico , Teofilina/administração & dosagem , Teofilina/metabolismoRESUMO
Em estudo duplo cego, aleatório, foi avaliado o comportamento de um preparado de teofilina de liberaçäo lenta (Teolong) administrado com dose oral única de 600 mg a voluntários normais. Foram estudadas: teofilina pela cromatologia líquida de alta eficiência (CLAE ou HPLC) antes e após intervalos variáveis da administraçäo da droga; tolerabilidade pelo questionário de efeitos colaterais e variáveis farmacocinéticas (constante de eliminaçäo - Kel; meia-vida beta - t1/2; volume de distribuiçäo - Vd; e clearance do organismo - CIB). Os resultados mostraram: ampla variaçäo interindividual da teofilinemia e na biodisponibilidade da droga. Todavia, a absorçäo do fármaco ocorreu de modo homogêneo, entre seis e oito horas, períodos de concentraçäo máxima, e sem, efeitos colaterais clínicos. Os autores lembram algumas condiçöes, como desnutriçäo, alcoolismo, etc., que poderiam influir na farmacocinética da droga e chamam a atençäo para a real necessidade da monitorizaçäo da teofilinemia durante o uso prolongado da droga
Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Teofilina/farmacologia , Método Duplo-Cego , Teofilina/administração & dosagem , Teofilina/metabolismoAssuntos
Adulto , Humanos , Masculino , Teofilina/metabolismo , Absorção Intestinal , Intubação GastrointestinalRESUMO
The single- and multiple-dose absorption characteristics of a new sustained-release theophylline preparation, which has been formulated for once per day dosing in adults, were investigated in children aged 8 to 14 years. Four single doses were studied, each dose separated by 1 week. During steady state the preparation was given once daily in the morning for 1 week, and serum theophylline concentration was determined through two dosing intervals (48 hours). The product showed excellent sustained-release characteristics and consistent absorption profiles, which were not affected to any clinically important extent by the intake of various meals. After single doses, only 77% to 91% of the product was absorbed during the first 28 hours after dosing. However, bioavailability was complete both after single doses and during steady state. Eight of 14 children had steady-state fluctuations in serum theophylline levels of less than 90% when given doses once daily. Steady-state day-to-day variations in serum theophylline profiles were small in all patients except one, in whom differences up to 33 mumol/L (6 micrograms/mL) were seen (8 hours after dosing). We conclude that this formulation is completely absorbed at a sufficiently slow and consistent rate to permit acceptable fluctuations in absorption with once daily dosing for many, but not all, patients. However, it should not be used in very young children until bioavailability has been studied in this age group.
Assuntos
Asma/metabolismo , Teofilina/metabolismo , Absorção , Adolescente , Asma/tratamento farmacológico , Disponibilidade Biológica , Criança , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Jejum , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Feminino , Humanos , Cinética , Masculino , Teofilina/administração & dosagem , Fatores de TempoRESUMO
A ocho niños con edades entre los 7 y 13 años se les administró teofilina bajo la forma de tabletas de liberación controlada (TEOBID)x100 mg, en dosis entre 10 y 15 mg/kg/día distribuida en dos tomas cada 12 horas, por cinco días consecutivos
Assuntos
Criança , Adolescente , Humanos , Asma/tratamento farmacológico , Teofilina/uso terapêutico , Cinética , Teofilina/metabolismoRESUMO
Una nueva forma de teofilina de liberación controlada (Producto A tabletas x 200 mg) fue evaluada en tres pacientes asmáticos: En un ensayo preliminar a los pacientes se les administró un bolo I.V. de aminofilina para determinar aclaración renal y la vida media, luego se practicó un estudio cruzado en modelo abierto con una sola dosis del producto en comparación con tabletas convencionales. En una segunda etapa a los pacientes se les administró el producto de liberación controlada cada 12 horas por cinco días consecutivos para determinar si la formulación era capaz de alcanzar y mantener un estado estacionario con niveles terapéuticos. En una tercera etapa los pacientes recibieron cada 12 horas un producto de liberación controlada muy conocido y de venta en U.S.A durante siete días al cabo de los cuales se les cambió la medicación al producto de liberación controlada en estudio manteniendo la misma dosis e intervalo de dosificación para establecer bioequivalencia. Los resultados de este estudio demostraron la utilidad del producto para el logro de niveles sanguíneos seguros y efectivos con un régimen de cada 12 horas. También se demostró que el producto en estado estacionario es bioequivalente con el otro producto de liberación controlada
Assuntos
Adulto , Humanos , Masculino , Feminino , Asma/tratamento farmacológico , Teofilina/uso terapêutico , Teofilina/metabolismoRESUMO
En doce humanos adultos, sanos, con edades entre los 19 y 31 años se evaluó, en forma secuencial cruzada, el comportamiento farmacocinético de una nueva preparación de teofilina de liberación controlada (Teobid tabletas x 200 mg) en comparación con una tableta convencional y otra formulación de liberación controlada, todas de 20 mg de concentración
Assuntos
Adulto , Humanos , Teofilina/metabolismoRESUMO
Many factors, including age and nutritional status, can affect drug metabolic rates. This study was designed to assess the metabolising capacity for the anti-asthmatic drug, theophylline, in malnourished elderly subjects before and after nutritional rehabilitation. Thirteen elderly, clinically malnourished subjects (aged 65-88 yrs.) were studied three to four days after admission to hospital for social reasons, and again after ten days of re-feeding with a high calorie, high protein diet. Theophylline half-life (T«) and clearance (CI) were determined from blood samples taken between 3 and 24 hours after a dose of 3.5 mg/kg. Malnutrition was assessed clinically and by serum albumin, haemoglobin and thyroid binding pre-albumin (TBPA). Serum albumin and TBPA were positively correlated and both increased after re-feeding. Theophylline Tu« and Cl values were within reported ranges. Half-lives were the same as those of healthy adult controls, but clearances were greater. Cigarette smokers were among the slowest, suggesting some other factor of malnutrition or acute hospitalisation may accelerate metabolism. On re-feeding, clearances increased by 37 percent, showing a great capacity of the elderly to respond to dietary supplementation; the subjects who were most malnourished had the lowest Cl rates and responded with the greates increase. These results have important implications for the selection of drug dose regimes for elderly hospitalised patients as the drug requirements may changed considerably during rehabilitation (AU)
Assuntos
Humanos , Idoso , Teofilina/metabolismo , Distúrbios NutricionaisRESUMO
Theophylline absorption from sustained-release formulations intended for administration every 8 hours and every 12 hours was examined in children ages 2 to 6 years during multiple dosing intervals. By generally applied measurements, including mean serum theophylline concentration, bioavailability over a single daytime dosing interval, and percent change in serum theophylline concentration over a single dosing interval, the preparations did not differ. However, over multiple dosing intervals, the 8-hour preparation varied in rate and extent of absorption, with subsequent large variations in serum theophylline concentrations. The 12-hour preparation, on the other hand, was completely bioavailable during each dosing interval, although the rate of absorption did differ from day to night, and was associated with generally acceptable changes in serum concentrations. Thus, analysis of dose-to-dose absorption was required to reveal the differences between the two study preparations. This indicates that traditional analysis of a single daytime dosing interval may be inadequate in the evaluation of preparations of sustained-release theophylline.