The effect of three different oral doses of verapamil on the disposition of theophylline

Results of previous studies suggest that the theophylline-verapamil drug interaction may be dependent on verapamil dose. Therefore, in a randomized four-way cross over study, 12 healthy males received theophylline, as a single intravenous dose of aminophylline, alone (phase I) and after a four day regimen of oral verapamil 40 mg (phase II), 80 mg (phase III), and 120 mg (phase IV) every 8 h. Serial blood samples were collected over a 24 hour period for determination of serum theophylline concentration and subsequent pharmacokinetic analysis. Mean theophylline AUC for phase I-IV was 93.6, 105.6, 110.8, 120.1 mg.h.l-1, respectively. Mean theophylline clearance for phase I-IV was 3.89, 3.59, 3.35, and 3.20 l.h-1, respectively. The changes in AUC, clearance, and lambda z were linearly correlated to verapamil dose. These results suggest that the inhibitory effect of verapamil on the pharmacokinetic disposition of theophylline is directly related to verapamil dose.