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.
Stringer
K A
KA
School of Pharmacy, University of Colorado Health Sciences Center, Denver.
Mallet
J
J
Clarke
M
M
Lindenfeld
J A
JA
D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D013806:Theophylline / Q000493:pharmacokinetics*; D014700:Verapamil / Q000008:administration & dosage* / Q000494:pharmacology
D013806:Theophylline; D014700:Verapamil