STEADY-STATE PHARMACOKINETICS OF THEOPHYLLINE IN COPD PATIENTS TREATED WITH DIRITHROMYCIN

Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a lo-day regimen of the macrolide antibiotic, dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (C(ss,min)) were invariant before, during, and after dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (C(av)) declined by 7% during dirithromycin treatment (NS), and mean peak plasma concentrations (C(ss,max)) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.