Depression of theophylline elimination by erythromycin

The elimination of a single oral dose of theophylline was studied in 12 healthy subjects before and after 250 mg erythromycin every 8 hr for 10 days. Serum theophylline levels were measured by high-pressure liquid chromatography. Mean theophylline elimination half-life rose from 4.79 ± 0.43 hr before to 7.53 ± 0.71 hr after erythromycin. Theophylline clearance decreased from a mean of 91.6 ± 27.0 to 54.8 ± 10.0 mllkg/hr after erythromycin and the mean apparent volumes of distribution were much the same before and after the antibiotic. The excretion of theophylline and its metabolites was studied in the urine of three of the subjects. In each case the amount of 3-methylxanthine and 1,3-dimethyluric acid decreased after antibiotic. Adjustments of the theophylline dosage may be necessary for patients who take theophylline and erythrgmycin concurrently to minimize the risk of theophylline toxicity.