In-vitro and in-vivo studies of the decrease of amphotericin B toxicity upon association with a triglyceride-rich emulsion.
The effects of amphotericin B associated with a triglyceride-rich emulsion (AB-emulsion), shown previously to behave like lymph chylomicrons, were evaluated in vitro and in vivo. Incorporation of amphotericin B to the emulsion was monitored by UV-visible spectrophotometry. Whilst conventional amphotericin B induced a considerable K+ efflux from erythrocytes, AB-emulsion had essentially no effect. In contrast, the K+ efflux from Candida albicans was similar upon incubation either with AB-emulsion or with conventional amphotericin B. Administration to rats showed reduced mortality due to AB-emulsion compared with conventional amphotericin B. Renal toxicity was also decreased upon AB-emulsion treatment, as evaluated by serum urea and creatinine levels. These data suggest that chylomicron-like emulsions could be utilized as vehicles for amphotericin B in antifungal therapy.
Souza
L C
LC
Faculdade de Ciências Farmacêuticas, University of São Paulo, Brazil.
Maranhão
R C
RC
Schreier
S
S
Campa
A
A
D000666:Amphotericin B / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers; D004655:Emulsions; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
D004337:Drug Carriers; D004655:Emulsions; D014280:Triglycerides; D000666:Amphotericin B