SERUM PHARMACOLOGY OF AMPHOTERICIN-B APPLIED IN LIPID EMULSIONS

Application of amphotericin B in lipid emulsions (AmB/L) reduced membr ane toxicity in vitro and decreased amphotericin B-associated toxic si de effects in vivo when compared to that of amphotericin B applied in 5% glucose (AmB/G). Therefore, a comparative analysis of the pharmacol ogical parameters of AmB/L and AmB/G was performed. Thirteen patients were analyzed, and nine of these patients received a subsequent treatm ent with AmB/G and AmB/L. In patients in both treatment groups amphote ricin B showed a biphasic elimination from serum, with a prolonged ter minal half-life of approximately 27 h. Patients treated with AmB/L sho wed significantly lower peak concentrations (44.2%; P = 0.008) and cor respondingly lower area under the drug concentration-time curve (AUG) values (61.3%; P = 0.015) compared to the values for the same patients treated with AmB/G at a dose range of 0.6 to 1.5 mg/kg of body weight , The enhanced clearance of AmB/L may be due to a faster initial elimi nation of amphotericin B-lipid aggregates by the reticuloendothelial s ystem. Lower peak concentrations and AUC values in serum and a corresp ondingly faster deposition of AmB/L in tissues may at least partly exp lain the lower toxicity of AmB/L, A comparative pharmacokinetic analys is with data for a single patient treated with AmB/L demonstrated that hemodialysis did not significantly affect the disposition of amphoter icin B.