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 < .05), and mean peak plasma concentrations (Css,max) declined by 26% (P < .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 < P < .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. 1990 American College of Clinical Pharmacology