Effect of erythromycin base on theophylline kinetics

Abstract

Because of several recent reports describing altered theophylline elimination in the presence of erythromycin salts, the effect of a 10 day course of erythromycin base on theophylline kinetics was studied in 8 healthy adult men. Theophylline (4 mg/kg) was given on 4 separate study days: prior to starting erythromycin, on the 3rd day of erythromycin administration, on the 10th day of erythromycin administration and 2 wk 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 l/kg; elimination half-life (t1/2), 7.4, 7.8, 8.5 and 7.0 h and total body clearance (ClB), 0.747, 0.723, 0.683 and 0.821 ml/min per kg. A maximum decrease of 20.7% in theophylline ClB was noted by the 3rd study day. Two wk after erythromycin was discontinued, the greatest increase in ClB observed was 45.7%. Differences in t1/2 and ClB between the 3rd and 4th study days were statistically significant (P < 0.05).