CONTROLLED-STUDY OF THE PUTATIVE INTERACTION BETWEEN FAMOTIDINE AND THEOPHYLLINE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

The effects of famotidine (80 mg per day), cimetidine (1600 mg per day ), and placebo an theophylline pharmacokinetic parameters in chronic o bstructive pulmonary disease (COPD) patients were compared, This was a n open-label, randomized, three-period crossover study, in which each subject first underwent a seven-day theophylline washout period, and t hereafter received three single intravenous doses of theophylline (5 m g/kg infused over 30 minutes) during the study. Each of the experiment al treatments was administered orally every 12 hours for a total of 9. 5 days (19 doses). Theophylline was infused after the 17th dose of eac h treatment. Fourteen serial blood samples were collected before the s tart of each infusion, and for 30 hours after the end of each infusion . Plasma samples were assayed for theophylline, pharmacokinetic parame ters were estimated, and treatment effects on each parameter were comp ared, Fourteen COPD patients completed all three periods of the invest igation. Famotidine treatment had virtually no effect on any of theoph ylline's pharmacokinetic parameters. In contrast, cimetidine treatment significantly altered every pharmacokinetic parameter of theophylline as follows: Cimetidine decreased theophylline geometric mean CL from 2.74 L/h to 2.07 L/h (P <.001), and prolonged theophylline harmonic me an half-life from 6.6 to 9.6 hours IP <.001) and mean residence time f rom 10.8 to 15.0 hours (P <.001). Cimetidine treatment slightly increa sed theophylline volume of distribution by approximately 10%, and that change also was statistically significant (P = .032). The authors con clude that the treatment effects of cimetidine on theophylline pharmac okinetic parameters were in accord with those reported by others, and that famotidine treatment had no effect on any of theophylline's pharm acokinetic parameters in COPD patients.