Erythromycin and 2'-acetyl erythromycin concentrations in plasma and pelvic tissues after repeated doses of erythromycin acistrate.

The concentrations of erythromycin (E) and 2'-acetyl erythromycin (2'-AE) in female pelvic organs, i.e. endometrium, myometrium, ovary and Fallopian tube, as well as in plasma, were determined after oral dosing of erythromycin acistrate (EA, CAS 96128-89-1), a erythromycin prodrug. Ten patients undergoing selective gynecological operation were given three doses of EA (400 mg) at 8-h intervals immediately before the operation. Tissue samples were taken 75-205 min after the intake of the last dose. Blood samples were collected immediately prior to and up to 8 h after the intake of the last dose. High total antibiotic (erythromycin + 2'-acetyl erythromycin) concentration in plasma were measured throughout the dose interval after the last dose. The concentrations of E in plasma were over the MICs for most of the erythromycin-sensitive bacteria (0.5 micrograms/ml) in 7 out of 10 patients (mean 0.66 micrograms/ml) at the end of the third dose interval. The drug concentrations in tissues were lower than in plasma (due to short treatment time of totally 24 h). The mean percentage of penetration (tissue/plasma ratios) for erythromycin ranged from 63 to 95% in various pelvic tissues. However, rather extensive interindividual variation was observed. The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 29-39% in plasma and 42-73% in tissue samples. There were negligible amounts of inactive anhydro forms in plasma after EA and their concentrations in tissue samples were low, as well.