The effects of erythromycin on the absorption and disposition of kinetics of theophylline.

The effects of erythromycin on the kinetics of theophylline were investigated in eight female patients with documented asthma in a crossover study. Theophylline pharmacokinetics were determined at steady state before and after one-week treatment with erythromycin stearate 250 mg given four times a day. Multiple serum samples were collected for 12 h after an aminophylline dose in the two drug treatment phases and assayed by high performance liquid chromatography. The resultant serum theophylline concentration-time data were analyzed by weighted, nonlinear regression analysis to obtain various pharmacokinetic parameters. In this study, the elimination half-live increased from 7.8 +/- 1.7 h on the control day to 9.5 +/- 1.4 h following treatment with antibiotic (p less than 0.02). The estimated apparent volume of distribution for theophylline (V/F) was also observed to increase from 0.42 +/- 0.09 l/kg before treatment with erythromycin to 0.53 +/- 0.15 l/kg after antibiotic treatment (0.05 less than p less than 0.10). In this study, no difference was demonstrated in the apparent clearance rate (Clapp), apparent first-order absorption rate constant (ka), maximum serum drug concentration (Cmax), time of maximum drug concentration (Tmax) or absorption lag time (tlag) for theophylline before and after treatment with erythromycin. With no apparent alteration in theophylline clearance following erythromycin coadministration, the decrease in the first-order elimination rate constant suggested that the apparent volume of distribution of theophylline is increased in the presence of erythromycin. It is concluded that patients maintained on theophylline derivatives should be closely monitored when erythromycin is coadministered.