Effect of erythromycin base on theophylline kinetics

Because of several recent reports describing altered theophylline elimination in the presence of salts of erythromycin, the effect of a 10-day course of erythromycin base on theophylline kinetics was studied in eight healthy adult men. Theophylline (4 mg/kg) was given on four separate study days: (1) prior to starting erythromycin, (2) on the third day of erythromycin administration, (3) on the tenth day of erythromycin administration, and (4) 2 weeks after the course of erythromycin was completed. Mean theophylline kinetic parameter values on each of the 4 study days were: apparent volume of distribution (Vd), 0.466, 0.466, 0.472, and 0.470 1/kg; elimination half-life (t1/2), 7.4, 7.8, 8.5, and 7.0 hr; and total body clearance (ClB), 0.747, 0.723, 0.683, and 0.821 ml/min/kg. A maximum decrease of 20.7% in theophylline ClB was noted by the third study day. Two weeks after erythromycin was discontinued, the greatest increase in ClB observed was 45.7%. Differences in t1/2 and ClB between the third and fourth study days were statistically significant (p less than 0.05).