Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation.
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.
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D002177:Candidiasis / Q000517:prevention & control; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009761:Nystatin / Q000494:pharmacology; D011090:Polyenes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013997:Time Factors; D014623:Vaginal Diseases / Q000517:prevention & control
D000935:Antifungal Agents; D011090:Polyenes; D009761:Nystatin; D000666:Amphotericin B