Effect of theophylline and enprofylline on bronchial hyperresponsiveness

Abstract

The effect of increasing intravenous doses of theophylline and enprofylline, a new xanthine derivative, on bronchial responsiveness to metacholine was studied in eight asthmatic patients. Metacholine provocations were carried out on three days before and after increasing doses of theophylline, enprofylline, and placebo, a double blind study design being used. Metacholine responsiveness was determined as the provocative concentration of metacholine causing a fall of 20% in FEV1 (PC20). The patients were characterised pharmacokinetically before the main study to provide an individual dosage scheme for each patient that would provide rapid steady state plasma concentration plateaus of 5, 10, and 15 mg/l for theophylline and 1.25, 2.5, and 3.75 mg/l for enprofylline. Dose increments in the main study were given at 90 minute intervals. FEV1 showed a small progressive decrease after placebo; it remained high in relation to placebo after both drugs and this effect was dose related. Methacholine PC20 values decreased after placebo; mean values were higher after theophylline and enprofylline than after placebo (maximum difference 2.0 and 1.7 doubling doses of metacholine); the effect of both drugs was dose related. Thus enprofylline and theophylline when given intravenously cause a small dose related increase in FEV1 and metacholine PC20 when compared with placebo.