EVALUATION OF RENAL TOXICITY AND ANTIFUNGAL ACTIVITY OF FREE AND LIPOSOMAL AMPHOTERICIN-B FOLLOWING A SINGLE INTRAVENOUS DOSE TO DIABETIC RATS WITH SYSTEMIC CANDIDIASIS

Since fungal infections are prevalent in diabetic patients, in whom tr eatment is often complicated by underlying renal disease and dyslipide mias, the purpose of the present study was to determine if the antifun gal activity and nephrotoxic effects of amphotericin B (AmB) and lipos omal AmB (L-AmB) are different in nondiabetic (normolipidemic) rats co mpared with those in diabetic (dyslipidemic) rats with systemic candid iasis, Nondiabetic and diabetic rats infected with Candida albicans re ceived a single intravenous dose of either AmB (0.8 mg of AmB per kg o f body weight), L-AmB (0.8, 2, or 4 mg of AmB per kg), or an equivalen t volume of normal saline (1 mi), Renal function was assessed by inuli n clearance, and antifungal activity was determined by measuring the n umbers of CFU of C, albicans that were present in the right kidney fol lowing drug treatment. AmB al 0.8 mg/kg and L-AmB at 0.8, 2, and 4 mg/ kg are effective antifungal agents in both diabetic and nondiabetic ra ts. However, while there was approximately a 4-fold decline in the mea n number of CFU per gram of kidney in nondiabetic rats, there was only approximately a 2.5-fold decline for the comparable dose (AmB, 0.8 mg /kg) in diabetic rats, There also appeared to be a similar fold reduct ion of L-AmB at all of the dosages tested, AmB treatment significantly improved renal function in diabetic and nondiabetic rats with systemi c candidiasis. Although L-AmB at all doses tested significantly improv ed renal function in diabetic rats with systemic candidiasis, only L-A mB at doses of 2 and 4 mg/kg significantly improved renal function in nondiabetic rats with systemic candidiasis, These findings suggest tha t following administration of a single intravenous dose, AmB and L-AmB appear to be less effective in killing C, albicans isolates in diabet ic than in nondiabetic rats, while they were found to improve the rena l functions of rats in both treatment groups.