THEOPHYLLINE-RANITIDINE INTERACTION IN ELDERLY COPD PATIENTS

Most controlled studies in humans indicate that ranitidine does not al ter theophylline metabolism, even at high doses. However, there have b een several case reports published recently which demonstrate the deve lopment of theophylline toxicity mostly in older patients receiving st able oral doses of this drug when ranitidine was administered simultan eously. We studied eleven elderly (mean age, 69.0 +/- 6.2 years) patie nts with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, follo wed by one week intake of the same dose of theophylline plus ranitidin e tablets, 150 mg every 12 h. At the end of each period, blood samples were obtained 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12 h after the morning do se for the determination of serum theophylline levels. The peak theoph ylline concentration (T-max) was achieved after 4.1 +/- 0.9 h while th e patients were taking theophylline, and after 2.9 +/- 1.4 h with the combined regimen. This difference was statistically significant (P<0.0 1). In only 3/11 subjects did T-max remain unchanged during both phase s of the study. The mean theophylline clearance rates while the patien ts were receiving theophylline alone (39.58 +/- 19.89 ml/min) and when they were receiving both medications (34.42 +/- 10.55 ml/min) were si milar. The mean serum levels while the patients were receiving theophy lline alone were slightly higher but not statistically different. Thes e results suggest that the reported increases in serum theophylline le vels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patient w ith COPD who is also given ranitidine.