RESUMO
OBJECTIVE: To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to severe persistent asthma. STUDY DESIGN: In our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, a total of 404 children with asthma, who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy, were randomly assigned to receive either 100, 200, or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline, mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to 123.3%) of the predicted normal value. RESULTS: Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo. Improvements were evident within 2 weeks and were maintained throughout the 12 weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function, and the incidence of reported adverse events was similar in all treatment groups. CONCLUSION: Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children (6 to 18 years of age) with moderate to severe persistent asthma.
Assuntos
Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Administração por Inalação , Administração Tópica , Adolescente , Anti-Inflamatórios/uso terapêutico , Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Hidrocortisona/sangue , Masculino , Nebulizadores e Vaporizadores , Pico do Fluxo Expiratório/efeitos dos fármacos , PósAssuntos
Asma/tratamento farmacológico , Teofilina/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Beclometasona/uso terapêutico , Broncodilatadores/uso terapêutico , Criança , Ensaios Clínicos como Assunto , Cromolina Sódica/uso terapêutico , Humanos , Metaproterenol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Teofilina/efeitos adversosRESUMO
Rapid glucocorticoid clearance and abnormal glucocorticoid receptor binding have been described as factors that contribute to an inadequate response to treatment with glucocorticoids in patients with asthma. We report the coexistence of these abnormalities in children with severe asthma who respond poorly to systemic glucocorticoid therapy.
Assuntos
Asma/tratamento farmacológico , Metilprednisolona/farmacocinética , Prednisolona/farmacocinética , Receptores de Glucocorticoides , Adolescente , Asma/metabolismo , Criança , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Metilprednisolona/uso terapêutico , Prednisolona/uso terapêuticoRESUMO
Prednisolone pharmacokinetics were evaluated in eight patients with cystic fibrosis (CF) (aged 1.8 to 20 years) by assessing absorption of orally administered prednisone (in its active form, prednisolone) and elimination of prednisolone after intravenous administration. After an overnight fast, subjects received intravenously administered doses of prednisolone or orally administered doses of prednisone, 40 mg/1.73 m2 body surface area, before a standardized breakfast. Serial blood samples were collected for 12 hours and analyzed for prednisolone concentration. Prednisolone pharmacokinetics were compared in eight age-matched patients with asthma who required steroids after intravenous administration of prednisolone. The prednisolone pharmacokinetic parameters derived demonstrated an increased total clearance (by 60%), an increased volume of distribution (by 46%), a lower peak concentration (by 35%), and no difference in elimination half-life in patients with CF compared with those with asthma. Bioavailability averaged 88.4% +/- 20.1% of the administered dose. Prednisolone clearance was markedly increased in those with CF. There was a proportional increase in nonrenal clearance, with no difference in renal clearance in those with asthma or CF. The plasma protein binding of prednisolone was only slightly decreased in patients with CF and did not account for the observed pharmacokinetic alteration. The marked increase in prednisolone clearance may necessitate the use of more frequent or higher doses of this steroid in the treatment of patients with CF, leading to a potentially less favorable benefit/risk ratio.
Assuntos
Fibrose Cística/metabolismo , Prednisolona/farmacocinética , Administração Oral , Asma/metabolismo , Disponibilidade Biológica , Criança , Humanos , Infusões Intravenosas , Prednisona/farmacocinéticaAssuntos
Asma/tratamento farmacológico , Comportamento Infantil/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Teofilina/efeitos adversos , Criança , Transtornos do Comportamento Infantil/induzido quimicamente , Depressão/induzido quimicamente , Humanos , Deficiências da Aprendizagem/induzido quimicamente , Teofilina/uso terapêuticoRESUMO
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.
Assuntos
Asma/tratamento farmacológico , Teofilina/metabolismo , Disponibilidade Biológica , Criança , Pré-Escolar , Preparações de Ação Retardada , Humanos , Absorção Intestinal , Cinética , Teofilina/administração & dosagem , Teofilina/uso terapêutico , Fatores de TempoRESUMO
During routine monitoring of hospitalized children with asthma receiving a sustained-release theophylline formulation, we frequently observe unpredictable fluctuations in serum theophylline concentration (STC). We evaluated eight asthmatic patients (ages 4 to 17 years) with inconsistent STCs to determine the cause of this phenomenon. Only minimal variation in STC and therefore theophylline clearance was noted during a 24-hour period of continuous intravenous aminophylline infusion. However, marked variability in STC was observed when measured every 2 hours for 48 hours after 6 days of continuous therapy orally. In addition, the time required to reach peak and trough STCs varied from dose to dose. Inasmuch as clearance was shown to be constant, the variability was attributed to inconsistent theophylline absorption. Unpredictable fluctuations of STC secondary to variable absorption from this sustained-release theophylline preparation may occur in certain patients. Appreciation of this potential variability is necessary for the proper interpretation of STC measurements and subsequent dosage adjustment.
Assuntos
Asma/metabolismo , Teofilina/metabolismo , Adolescente , Aminofilina/administração & dosagem , Asma/tratamento farmacológico , Disponibilidade Biológica , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Preparações de Ação Retardada , Feminino , Meia-Vida , Humanos , Infusões Parenterais , Absorção Intestinal , Cinética , Masculino , Comprimidos , Teofilina/administração & dosagem , Teofilina/sangueRESUMO
Serum digoxin values were determined in a newborn infant with severe heart failure and renal failure. The half-life of digoxin in the serum appeared to change, possibly the result of prolonged distribution and/or absorption owing to circulatory insufficiency, or to the accumulation of cross-reacting metabolites of digoxin in the serum. No clinical toxicity was apparent, and no cardiac arrhythmia was observed. The need for monitoring serum digoxin concentration and clinical effect in newborn infants is emphasized.