Enprofylline: Pharmacokinetics and comparison with theophylline of acute effects on bronchial reactivity in normal subjects

Summary In a double blind, placebo controlled, crossover study the pharmacokinetics and acute effects of enprofylline and theophylline on airway reactivity during histamine challenge were investigated in 10 healthy volunteers. The pharmacokinetic parameters of enprofylline were (mean): elimination half-life 1.9 h, total body clearance 191.1 ml · kg^–1 · h^–1, volume of distribution 0.48 l · kg^–1, and protein binding 49%. Bronchial reactivity in the histamine inhalation test was expressed as the concentration causing a 20% fall in FEV_1.0 (PC₂₀). Mean PC₂₀ values were lowest after placebo and highest after theophylline with the enprofylline values in between. Only the difference in PC₂₀^Safter placebo and theophylline was statistically significant (p<0.05). At the time of determination of the PC₂₀, the serum concentration of enprofylline was between 16.5 and 11.8 µmol/l, and that of theophylline was between 78.3 and 61.1 µmol/l. Adverse actions of enprofylline were nausea (3/10) and cardiovascular reactions (2/10), whereas theophylline mainly caused restlessness (3/10) and tremor (2/10). Thus enprofylline, in one-fifth of the serum concentration of theophylline cannot be regarded as equipotent in terms of bronchoprotection.In fulfillment of his thesis (Dr. med.)