The Effect of Erythromycin on Theophylline Pharmacokinetics in Chronic Bronchitis1,2

Abstract

We examined theophylline pharmacokinetics for changes caused by the addition of erythromycin in patients with chronic bronchitis and obstructive pulmonary disease. Twelve hospitalized patients were randomized in a crossover fashion to receive aminophylline and either erythromycin or placebo. After the eighth dose, plasma was analyzed for theophylline, using the enzyme-mediated immunoassay technique. A 6-h urine collection was analyzed for theophylline metabolites, using high-pressure liquid chromatography. Erythromycin significantly decreased mean theophylline clearance by 22% from 4.9 L/min to 3.87 L/min in (p < 0.05). Mean peak theophylline levels increased 28% from 11.9 μg/ml to 15.3 μg/ml (p = 0.05). No change in urine theophylline metabolites was found. Patients with chronic bronchitis and obstructive pulmonary disease who begin erythromycin while receiving a preexisting therapeutic theophylline regimen experience a significant elevation of theophylline concentration, which predisposes to theophylline toxicity. For those patients with theophylline levels at the higher end of the therapeutic range (15 to 20 μg/ml), we recommend an initial 25% reduction in theophylline dosage when erythromycin is added. Serum theophylline levels should be monitored for further refinement of dosage.