Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation
| Autor: | Claude Vezina, Anne Marie Sidorowicz, S. N. Sehgal, H. Baker |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Male
Nystatin Antifungal Agents Time Factors medicine.drug_class Vaginal Diseases Antibiotics Biological Availability Polyenes Biology Pharmacology Mice Subcutaneous injection Dogs Oral administration In vivo Amphotericin B Drug Discovery medicine Animals Antifungal antibiotic Candidiasis Hydrogen-Ion Concentration Corpus albicans Rats Female medicine.drug |
| Zdroj: | The Journal of Antibiotics. 31:539-545 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.7164/antibiotics.31.539 |
| Popis: | The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration. Rapamycin cured systemic candidosis in mice: PD50 s.c. was 9.5 mg/kg: PD50 p.o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment. |
| Databáze: | OpenAIRE |
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