The effect of verapamil on the pharmacokinetic disposition of theophylline in cigarette smokers

Abstract

In a randomized cross-over study the effect of verapamil on the pharmacokinetics of theophylline was evaluated in eight cigarette smoking male volunteers. Theophylline was administered as an intravenous infusion of aminophylline, 6 mg/kg based on ideal body weight, over 30 minutes in the control phase. In the treatment phase, aminophylline was administered after a four day regimen of oral verapamil 80 mg every 8 hours. Serial blood samples were collected over a 24 hour period following aminophylline administration. Theophylline serum concentrations were determined by a fluorescence polarization immunoassay, the Abbott TDxR. Theophylline clearance decreased by 11.5%, from a mean (+/-SD) of 1.39 +/- 0.38 mL/min/kg in the control phase to 1.23 +/- 0.21 mL/min/kg with the co-administration of verapamil (P = 0.104). Theophylline elimination rate constant decreased by approximately 9.4% from 0.171 +/- 0.032 to 0.155 + 0.023 hr-1 during the treatment phase (P = 0.085). The area under the curve (AUCo alpha) and volume of distribution at steady-state (Vss) for theophylline were also not statistically different between the two study phases. These results are inconsistent with those of other investigators and the relevance of a potential theophylline-verapamil drug interaction remains unclear.