Theophylline-ranitidine interaction in elderly COPD patients

Abstract

Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses. However, there have been several case reports published recently which demonstrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously. We studied eleven elderly (mean age, 69.0 +/- 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, followed by one week intake of the same dose of theophylline plus ranitidine 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 dose for the determination of serum theophylline levels. The peak theophylline concentration (Tmax) was achieved after 4.1 +/- 0.9 h while the patients were taking theophylline, and after 2.9 +/- 1.4 h with the combined regimen. This difference was statistically significant (P < 0.01). In only 3/11 subjects did Tmax remain unchanged during both phases of the study. The mean theophylline clearance rates while the patients were receiving theophylline alone (39.58 +/- 19.89 ml/min) and when they were receiving both medications (34.42 +/- 10.55 ml/min) were similar. The mean serum levels while the patients were receiving theophylline alone were slightly higher but not statistically different. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patients with COPD who is also given ranitidine.