Fate of single oral doses of erythromycin acistrate, erythromycin stearate and pelleted erythromycin base analysed by mass-spectrometry in plasma of healthy human volunteers.

Abstract

The kinetics of erythromycin acistrate (EA). a new ester prodrug of erythromycin, were studied in three comparative, randomized, cross-over studies in 29 healthy volunteers. A new mass-spectrometric method was used to assay separately erythromycin, 2'-acetyl erythromycin and their anhydro (spiroketal) forms. In Part I, the total antibiotic concentration was higher after EA than after erythromycin stearate (ES; 1.8-fold) and enterocoated pellets of erythromycin base (EB, enterocapsules; 1.4-fold). In plasma, however, only about one third of 2'-acetyl erythromycin was hydrolysed to active erythromycin. Moreover, after unprotected EA tablets, a considerable proportion of erythromycin and 2'-acetyl erythromycin was inactivated by gastric acid as reflected by high concentrations of respective anhydro (spiroketal) forms. In Part II, the unprotected (regular tablets) and acid-protected tablets (dissolution starts at pH 4.5) were compared. The protected tablet, albeit not an enterotablet, was not destroyed by gastric acid. Its absorption was slightly delayed but the bioavailability was good. In this study, the absorption of total antibiotic was 2.8-fold (unprotected tablet) and 3.9-fold (protected tablet) that after enterocapsules. In Part III, the bioavailabilities of 200 and 400 mg tablets (both acid-protected) were equal.