Pharmacokinetics of Erythromycin on Repetitive Dosing

Serum erythromycin concentration data from several repetitive dosing studies were analyzed with newly developed computer methods for fitting multiple-dose data and generating nonlinear least-squares estimates of pharmacokinetic parameters. This analysis indicates that the pharmacokinetics of erythromycin can be described by a one-compartment linear model with the following characteristics: (a) a lag time between the time of drug administration and the onset of absorption; (b) apparent zero-order rather than first-order absorption; (c) dose-to-dose variability in the rate and extent of absorption; and (d) day-to-day variability in the kinetics of elimination. The bioavailability of the third dose of erythromycin on a given day is considerably lower than that of the second dose or of the fourth and last dose of the day. The average apparent half-life of erythromycin was 1.8 hour on day 1 and 2.6 hours on day 3 of the repetitive dosing regimen.