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-controlled, 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: theophylline + 200 mg nefazodone twice daily (every 12h) and theophylline+matching nefazodone placebo capsule twice daily (every 12h). Mean peak and trough plasma concentrations of theophylline ranged from 13.1 to 14.5 micrograms ml-1 and 11.6 to 14.2 micrograms ml-1, respectively, at steady-state when theophylline was administered with or without concurrent dosing of nefazodone. Similarly, the mean area under the curve for theophylline ranged from 93.5 to 103 micrograms ml-1 h. When nefazodone and theophylline were co-administered, theophylline pharmacokinetic parameters did not significantly differ from those obtained when theophylline was administered with placebo. Forced expiratory volume in one second (FEV1) measurements taken when nefazodone or placebo were administered with theophylline did not differ from those obtained at baseline. The plasma concentration-time profiles for nefazodone and its metabolites were similar to those in other studies where nefazodone was administered alone. Since nefazodone did not affect the pharmacokinetics or the pharmacodynamics of theophylline, no change in theophylline dose should be needed as a consequence of nefazodone co-administration.
Dockens
R C
RC
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Rapoport
D
D
Roberts
D
D
Greene
D S
DS
Barbhaiya
R H
RH
D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D010879:Piperazines; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D000928:Antidepressive Agents; D001993:Bronchodilator Agents; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone; D013806:Theophylline