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V Rauramaa

Publications and source records attributed to V Rauramaa.

4 recordsLinked to original sources
PubMed1989

Efficacy of erythromycin acistrate (2'-acetyl erythromycin stearate) and erythromycin stearate in experimental infections in mice.

The efficacy of erythromycin stearate (ES) and its 2'-acetyl ester (erythromycin acistrate, EA) was compared in eight experimental infections in mice of both sexes. In two studies the mice were made leukopenic by whole-body irradiation. Four absorption studies were also performed in parallel. In Streptococcus pneumoniae peritonitis, the protective dose 50% (PD50) value of EA and ES, given s.c., did not differ from each other. The bioavailability of EA was slightly inferior to that of ES. In three other peritonitis studies (2 Staphylococci and 1 Streptococcus), where the treatments were given s.c., EA seemed to lag behind ES in efficacy. The parallel absorption experiment showed, however, that, as compared to ES, only about one-half of EA was released from the s.c. injection site to the blood. The adjusted PD50 values of both erythromycins were about the same, with one exception. When the treatments were given i.p. both erythromycins were equally effective, and the difference in bioavailability was minor. On the contrary, the efficacy of 2'-ethylsuccinyl erythromycin was only about one-tenth that of the other erythromycins as was also the bioavailability. Oral treatment gave similar therapeutic results with EA and ES, with similar bioavailabilities, too. In the muscle abscess model, single s.c. injections of EA and ES were equally effective in reducing the growth of Staphylococcus aureus. These results suggest that there is no great difference in the in vivo antibacterial performance of ES and its 2'-acetyl ester, although the absorption problems complicate the interpretation. Hence EA performs better than expected if only the hydrolyzed drug were useful.

Animals↗
PubMed1988

Concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms in plasma and tonsillar tissue after repeated dosage of erythromycin stearate and erythromycin acistrate.

The concentrations of erythromycin, 2'-acetylerythromycin (2'-AE) and their anhydro forms in plasma and tonsillar tissue were analyzed after a 3-day repeated-dosage regimen of erythromycin stearate (ES; 500 mg twice a day [b.i.d]) and erythromycin acistrate (EA), a new erythromycin prodrug, at two doses (400 and 500 mg b.i.d.). The tonsils of 40 patients were removed at 112 to 329 min after intake of the last dose. Blood samples were collected at the time of tonsillectomy and at 0, 2, and 6 h after the last dose. At all time points, EA produced severalfold more total antibiotic (erythromycin + 2'-AE) concentrations in plasma compared with ES. There were two nonabsorbers in the ES group, but none in the two EA groups. The mean total antibiotic levels in tonsillar tissue after EA treatment exceeded the levels after treatment with ES by a factor of 3 (for EA at 400 mg b.i.d.) and 4.5 (for EA at 500 mg b.i.d.). The ratios of erythromycin concentration in tonsil to that in plasma at the time of tissue removal were quite similar for all groups (means, 0.51 to 0.54). In the EA groups, 2 of 26 (8%) patients had no measurable erythromycin in the tonsillar tissue samples, whereas in the ES group, 3 of 14 (21%) patients had no measurable erythromycin in the same tissue. The degree of hydrolysis of 2'-AE to erythromycin was about 25% in plasma at the time of tonsillectomy for both EA groups and about 40% in tonsillar tissue. There were negligible amounts of anhydro forms in plasma after EA administration, whereas in the ES group, anhydroerythromycin levels were, from time to time, even higher than erythromycin levels. Very high levels of anhydro forms were detected in tonsillar tissue after ES treatment, whereas only low levels were found after EA administration.

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