Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats.

Abstract

The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined. After 6 days of daily intraperitoneal injections of AmB-DC, decreased body weight and glomerular filtration rate as well as increased degree of diuresis, uremia, microalbuminuria, and N-acetyl-beta-D-glucosaminidase excretion in urine were noted. Urinary excretion of potassium and sodium was also decreased in AmB-DC-treated rats. Most of these effects were more pronounced with AmB-PC and AmB-SA50. In contrast, AmB-Myrj 59 was less nephrotoxic than AmB-DC. Indeed, after 6 days of treatment with AmB-Myrj 59, the natriuria, kaliuria, albuminuria, and glomerular filtration rates were unchanged compared with those of controls. Moreover, the body weight loss and uremia increase of the rats treated by AmB-Myrj 59 were less than those of the rats treated with the commercial preparation. Among the surfactants, only PC was toxic for the rats. The intrinsic toxicity of PC and the higher systemic exposure to AmB could contribute to increased toxicities of AmB-PC and AmB-SA50, respectively. AmB-Myrj 59 was less nephrotoxic than AmB-DC at equivalent areas under the plasma concentration-time curves. These preliminary results suggest that this formulation could be a good alternative to the commercial product.

• Authors: C Tasset, V Preat, A Bernard, M Roland
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 36 Issue 7 Pg. 1525-31 (Jul 1992) ISSN: 0066-4804 [Print] United States
• PMID: 1510450 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Drug Carriers
• Polyethylene Glycols
• Amphotericin B
• Sodium
• Potassium

Topics

• Amphotericin B (administration & dosage, blood, pharmacokinetics)
• Animals
• Body Weight (drug effects)
• Drug Carriers
• Glomerular Filtration Rate (drug effects)
• Injections, Intraperitoneal
• Kidney (drug effects, metabolism)
• Male
• Polyethylene Glycols (toxicity)
• Potassium (urine)
• Rats
• Rats, Inbred Strains
• Sodium (urine)