Changes in the steady-state pharmacokinetics of theophylline during treatment with dirithromycin

The steady-state plasma concentrations and pharmacokinetic characteristics of theophylline were studied during intermittent treatment with dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (200 mg every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline. Mean steady-state plasma theophylline trough concentrations (Cmin) were invariant before, during, and after dirithromycin treatment; however, mean average steady-state plasma theophylline concentrations (Cav) declined by 18% during dirithromycin treatment (P less than .05), and mean peak plasma concentrations (Css,max) declined by 26% (P less than .01). Theophylline clearance (CL/F) exhibited an increase of comparable magnitude during dirithromycin treatment, although the increase in CL/F was not statistically significant (.05 less than P less than .1). Dirithromycin treatment alters the steady-state pharmacokinetics of theophylline; however, the magnitude of the changes is small and is not likely to modify treatment outcomes.