Lack of effect of dirithromycin on theophylline pharmacokinetics in healthy volunteers

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) alone and after a 10 day course of dirithromycin (two 250 mg tablets ed). The study phases were separated by a 3 week washout period. Serum samples were collected before and for 24 h after theophylline doses. Serum theophylline concentrations were measured via a validated immunoassay system and the data were modelled via non-compartmental analysis. When the control phase (i.e. no dirithromycin) was compared with the treatment phase (i.e. with dirithromycin), theophylline exposures as measured by AUC(0->infinity) were not significantly different: 141.7 +/- 25.9 and 136.4 +/- 33.1 mg.h/L respectively (P = 0.16). No significant changes in other theophylline pharmacokinetic parameters were evident. These results indicate that theophylline can be safely cc-administered with dirithromycin.