The Effect of Verapamil on the Pharmacokinetic Disposition of Theophylline in Cigarette Smokers

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 TDx^R. 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 (AUC_0‐∞) 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. 1989 American College of Clinical Pharmacology