LACK OF AN EFFECT OF NEFAZODONE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF THEOPHYLLINE DURING CONCURRENT ADMINISTRATION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

The effect of nefazodone on the pharmacokinetics and pharmacodynamics of theophylline was evaluated in a multiple-dose, randomized placebo-c ontrolled, double-blind two-period crossover study in 13 patients who were undergoing theophylline therapy for chronic obstructive pulmonary disease. Two treatments were administered, each for 7 days: theophyll ine + 200 mg nefazodone twice daily (every 12h) and theophylline + mat ching nefazodone placebo capsule twice daily (every 12h). Mean peak an d trough plasma concentrations of theophylline ranged from 13.1 to 14. 5 mu g ml(-1) and 11.6 to 14.2 mu g ml(-1), respectively, at steady-st ate when theophylline was administered with or without concurrent dosi ng of nefazodone. Similarly, the mean area under the curve for theophy lline ranged from 93.5 to 103 mu g ml(-1) h. When nefazodone and theop hylline were coadministered, theophylline pharmacokinetic parameters d id not significantly differ from those obtained when theophylline was administered with placebo. Forced expiratory volume in one second (FEV (1)) measurements taken when nefazodone or placebo were administered w ith theophylline did not differ from those obtained at baseline. The p lasma concentration-time profiles for nefazodone and its metabolites w ere similar to those in other studies where nefazodone was administere d alone. Since nefazodone did not affect the pharmacokinetics or the p harmacodynamics of theophylline, no change in theophylline dose should be needed as a consequence of nefazodone co-administration.