Variability in the absorption and disposition of erythromycin estolate in humans.
The inter- and intrapersonal variability in the absorption and disposition of erythromycin estolate in humans was assessed by comparing total erythromycin serum concentrations in five subjects who each received a single erythromycin estolate tablet on three separate occasions under identical experimental conditions. Coefficients of variation for the pharmacokinetic parameters Cmax, Tmax, AUC0-12, MRT, and t1/2 were of a similar magnitude when calculated between subjects in any one administration phase or between phases. In addition, serum concentrations of both erythromycin base (active component) and erythromycin propionate were selectively determined in the same subjects only during the final two phases of the study. Comparison of AUC0-12 values showed that the percentage of the total area (base and ester components) present as erythromycin base remained relatively constant between administrations (mean values of 14.5 and 11.2%), with low coefficients of variation between subjects (10.8 and 11.6%). Discrepancy value calculations revealed that the variability in serum concentration-time profiles between the three phases of the study fell into the "small"-to-"moderate" classification. From these data it is apparent that intrapersonal variations in the absorption and disposition of erythromycin estolate are of a similar magnitude to interpersonal variations and should be borne in mind in the design and interpretation of comparative bioavailability studies involving similar formulations of this compound. The relative proportions of erythromycin base and propionate did, however, remain fairly constant both between treatments and between subjects.
Stubbs
C
C
School of Pharmaceutical Sciences, Rhodes University, Grahamstown, South Africa.
Kanfer
I
I
D000328:Adult; D001682:Biological Availability; D004917:Erythromycin / Q000031:analogs & derivatives*; D004918:Erythromycin Estolate / Q000493:pharmacokinetics*; D006801:Humans; D007206:Individuality; D007408:Intestinal Absorption; D008297:Male; D014018:Tissue Distribution
D004917:Erythromycin; D004918:Erythromycin Estolate