Amphotericin B lipid complex (ABLC) was recently approved by the Food and D
rug Administration for treatment of patients with invasive fungal infection
s who are intolerant of or refractory to conventional amphotericin B therap
y. Little is known, however, about the pharmacokinetics of this new antifun
gal compound. We therefore investigated the pharmacokinetics of ABLC in com
parison with those of conventional desoxycholate amphotericin B (DAmB) in r
abbits. The pharmacokinetics of DAmB in a rabbit model were similar to thos
e previously reported in humans. The pharmacokinetics of ABLC differed subs
tantially from those of DAmB. Plasma amphotericin B levels following ABLC a
dministration were 10 times lower than those following administration of an
equal dosage of DAmB. The levels of ABLC in whole blood were approximately
40 times greater than those in plasma. The ABLC model differed from the DA
mB model by (i) a dose- and time-dependent uptake and return between the pl
asma compartment and apparent cellular components of the blood-sediment com
partment and (ii) time-dependent tissue uptake and return to plasma from se
rially connected compartments. Following infusion of ABLC, there was a nonl
inear uptake into the apparent cellular components of the blood-sediment co
mpartment. This uptake was related to the reciprocal of the integral of the
total amount of drug infused (i.e., the more drug infused the greater the
fractional uptake between 0.5 and 5 mg/kg of body weight for ABLC). The tra
nsfer of drug from plasma to the cellular components of the blood-sediment
compartment resulted in initial uptake followed by rapid redistribution bac
k to the plasma. The study describes a detailed model of the pharmacokineti
cs of ABLC and characterizes a potential role of the cellular components of
the blood-sediment compartment in the distribution of this new antifungal
compound in tissue.