ABSTRACT
Enprofylline, a recently developed xanthine derivative, is a more potent bronchodilator than theophylline. This study compares the efficacy and safety of enprofylline with theophylline for chronic obstructive airways disease (COAD) in elderly subjects. The study was of a randomized double-blind parallel design and commenced with a 1-week reference period when oral bronchodilators were withdrawn. Patients were then treated with either enprofylline or theophylline 150 mg bd for 2 weeks (period 1) followed by 300 mg bd for a further 3 weeks (period 2). Patients recorded peak expiratory flow rate (PEFR) and adverse experiences, if any, in a diary, daily. Of 111 patients recruited for the study, 85 entered active treatment (theophylline, n = 44; enprofylline, n = 41). Mean age was 72 years and mean bronchodilator reversibility was 22%. Enprofylline increased mean morning PEFR by 11% (period 1) and 19% (period 2) whereas theophylline increased PEFR by 13% and 19%, respectively. From the enprofylline group 29% were withdrawn from the study due mainly to headache and nausea/vomiting and from the theophylline group 7% were withdrawn due mainly to nausea/vomiting. Mean plasma concentrations of enprofylline were 2.0 mg l-1 and 3.4 mg l-1, and with theophylline 5.4 mg l-1 and 10.0 mg l-1 at the end of periods 1 and 2, respectively. Enprofylline and theophylline produced similar improvements in lung functions and symptoms of chronic obstructive airways disease, but enprofylline was less well tolerated than theophylline.
Subject(s)
Bronchodilator Agents/therapeutic use , Lung Diseases, Obstructive/drug therapy , Theophylline/therapeutic use , Xanthines/therapeutic use , Aged , Double-Blind Method , Female , Headache/chemically induced , Humans , Lung Diseases, Obstructive/physiopathology , Male , Peak Expiratory Flow Rate/drug effects , Theophylline/adverse effects , Xanthines/adverse effectsABSTRACT
A patient with Addison's disease required increased corticosteroid dosage whilst receiving rifampicin. The pharmacological half-life of cortisol was reduced, but returned to normal when rifampicin was stopped. Cortisolproduction rates in four patients with pulmonary tuberculosis rose during treatment with rifampicin, as did urinary D-glucaric-acid excretion, an index of liver microsomal-enzyme activity. The alteration of the corticosteroid requirement in the patient with Addison's disease and the elevation of the cortisol-production rates were attributed to increased cortisol catabolism following hepatic macrosomal-enzyme induction by rifampicin.
