Induction of theophylline toxicity and inhibition of clearance rates by ranitidine.

PURPOSE

Theophylline is metabolized by the hepatic microsomal oxidase system, as is ranitidine, although the latter has a much lower affinity for the system. The incidence of theophylline toxicity is rare when the two drugs are administered simultaneously. We observed the development of clinical and chemical toxicity in three elderly patients receiving oral theophylline therapy for chronic obstructive pulmonary disease after the administration of ranitidine therapy for peptic ulcer disease.

PATIENTS AND METHODS

Three patients with chronic obstructive pulmonary disease who had been receiving theophylline for prolonged periods of time were studied. Two patients presented with complaints of epigastric pain, which was attributed to acid-peptic disease; the other patient presented with hematemesis, which was shown to be due to gastric and duodenal ulcers. Ranitidine was administered for treatment of acid-peptic disease. Theophylline clearance rates were determined before, during, and after ranitidine treatment. When symptoms of theophylline toxicity developed, the dose of theophylline was either stopped or reduced. Subsequently, patients were readministered their usual dose of theophylline.

RESULTS

The effect of simultaneous administration of both drugs resulted in similar reductions in theophylline clearance rates. Serum theophylline levels returned to pretreatment values after cessation of ranitidine treatment. In one patient, rechallenge with ranitidine during steady-state theophylline treatment resulted in recurrence of clinical and chemical theophylline toxicity.

CONCLUSION

These observations suggest that treatment with ranitidine may cause clinically apparent interactions with theophylline since both drugs are metabolized by the same cytochrome P-450 isozymes.