ABSTRACT
The pharmacokinetics of erythromycin estolate (500 mg) and erythromycin ethylsuccinate (600 mg) were compared in 12 healthy volunteers after single doses and after repeated oral doses (every 8 h). High-pressure liquid chromatography with electrochemical detection was used to determine concentrations in plasma and urine of estolate, ethylsuccinate, and erythromycin base. The maximum concentration of drug in the serum, the half-life, and the area under the curve for erythromycin estolate were significantly greater than those of erythromycin ethylsuccinate after both regimens. After single and multiple doses, the respective areas under the curve of erythromycin base generated by estolate formulation were 3 and 1.6 times greater (P less than 0.05) than those of ethylsuccinate. The lower percentage of hydrolysis of erythromycin estolate (41 versus 69%) combined with its longer half-life (5.47 versus 2.72 h) and its larger area under the curve (30.61 versus 4.68 micrograms/h/ml, after multiple doses) could explain these differences. This study underscores the need for a specific high-pressure liquid chromatography assay and the importance of wide variability, rate-limited processes, changes with multiple doses, and the appearance of a second peak when one studies the pharmacokinetics of erythromycin esters. The pharmacokinetic data presented in this study reinforce the clinical advantages of erythromycin estolate over erythromycin ethylsuccinate.
Subject(s)
Erythromycin Estolate/pharmacokinetics , Erythromycin/analogs & derivatives , Administration, Oral , Adult , Chromatography, High Pressure Liquid , Erythromycin/blood , Erythromycin/pharmacokinetics , Erythromycin/urine , Erythromycin Estolate/blood , Erythromycin Estolate/urine , Erythromycin Ethylsuccinate , Female , Humans , Male , Random AllocationABSTRACT
A high-performance liquid chromatographic analysis of erythromycin and its esters in plasma, urine and saliva is presented. A diethyl ether extract of sample was chromatographed on a reversed-phase column and components of the column effluent were monitored by electrochemical detection at +0.9 V (vs. Ag/AgCl). The method sensitivity limit was 10 ng with inter-day coefficients of variation from 3.2 to 10.3%. In order to assess precisely the relative concentrations of erythromycin esters (ethylsuccinate or estolate) and their active by-product erythromycin base, it is necessary to adopt measures preventing their continuous hydrolysis in biological fluids and during sample preparation.
Subject(s)
Erythromycin/analysis , Chromatography, High Pressure Liquid , Drug Stability , Electrochemistry , Erythromycin/analogs & derivatives , Erythromycin/blood , Erythromycin/urine , Erythromycin Estolate/analysis , Erythromycin Estolate/blood , Erythromycin Estolate/urine , Erythromycin Ethylsuccinate , Half-Life , Humans , Saliva/analysisABSTRACT
The absorption, excretion, and metabolism of [1-14C]lauryl sulfate as either the sodium or propionyl erythromycin salt has been studied in the rat and man. In the rat 88% of the radiolabel from propionyl erythromycin [1-14C]lauryl sulfate was excreted in the urine in the 24-hr period following a single oral dose. More than 95% of the radiolabel was excreted as the metabolite butyric acid 4-sulfate. This metabolite was shown to be derived from carbons 1-4 of the lauryl sulfate moiety. There was no evidence of sulfate cleavage in the rat. In man 51-59% of the administered ratioactivity was recovered in the urine. The major excretion product was butyric acid 4-sulfate accounting for approximately 95% of urinary radioactivity. The remainder was unchanged lauryl sulfate. A significant portion of the radiolabeled propionyl erythromycin lauryl sulfate was converted to 14CO2 indicating that the sulfate linkage was cleaved. A minimum value of 9-16% of the dose was metabolized in this manner.
