Premium
Controlled Study of the Putative Interaction Between Famotidine and Theophylline in Patients with Chronic Obstructive Pulmonary Disease
Author(s) -
Bachmann Kenneth,
Sullivan Timothy J.,
Reese James H.,
Jauregui Luis,
Miller Kristen,
Scott Mary,
Yeh K. C.,
Stepanavage Michael,
King Joyce D.,
Schwartz Jules
Publication year - 1995
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1995.tb04100.x
Subject(s) - theophylline , cimetidine , pharmacokinetics , famotidine , medicine , volume of distribution , copd , placebo , anesthesia , bronchodilator , histamine h2 receptor , asthma , pharmacology , antagonist , alternative medicine , receptor , pathology
The effects of famotidine (80 mg per day), cimetidine (1600 mg per day), and placebo on theophylline pharmacokinetic parameters in chronic obstructive pulmonary disease (COPD) patients were compared. This was an open‐label, randomized, three‐period crossover study, in which each subject first underwent a seven‐day theophylline washout period, and thereafter received three single intravenous doses of theophylline (5 mg/kg infused over 30 minutes) during the study. Each of the experimental treatments was administered orally every 12 hours for a total of 9.5 days (19 doses). Theophylline was infused after the 17th dose of each treatment. Fourteen serial blood samples were collected before the start of each infusion, and for 30 hours after the end of each infusion. Plasma samples were assayed for theophylline, pharmacokinetic parameters were estimated, and treatment effects on each parameter were compared. Fourteen COPD patients completed all three periods of the investigation. Famotidine treatment had virtually no effect on any of theophylline'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 mean half‐life from 6.6 to 9.6 hours ( P < .001) and mean residence time from 10.8 to 15.0 hours ( P < .001). Cimetidine treatment slightly increased theophylline volume of distribution by approximately 10%, and that change also was statistically significant ( P = .032). The authors conclude that the treatment effects of cimetidine on theophylline pharmacokinetic parameters were in accord with those reported by others, and that famotidine treatment had no effect on any of theophylline's pharmacokinetic parameters in COPD patients .