Clinical and pharmacokinetic evaluation of a new lipid-based delivery system of amphotericin B in AIDS patients.

To evaluate the safety, tolerance and pharmacokinetics of a new formulation of amphotericin B (AmB; CAS 1397-89-3) 18 AIDS patients treated for different kinds of mycoses were studied: oropharingeal and/or esophageal azole-resistant candidiasis (9), CNS cryptococcosis (7) or aspergillosis (2). Amphotericin B daily dose was infused in 100 ml of a lipid emulsion. The patients aged from 26 to 54 years with body weight ranging from 42 to 89 kg. Blood samples were collected at fixed intervals and plasma stored at -20 degrees C until tested by a specific HPLC assay. The individual kinetic analysis of plasma drug levels was performed by a two-compartment open model. The data were analyzed using P-Pharm, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The effect of a variety of demographic factors on clearance and volume of distribution was investigated. The clearance and the apparent volume of distribution were, respectively, (mean +/- SD): 0.037 +/- 0.015 l/h/kg and 0.45 +/- 0.32 l/kg. The interindividual variability in AmB clearance and volume of distribution was modelled with proportional error with an estimated coefficient of variation of 40.6% and 70.9%, respectively. Clinical and biological tolerance was very good and no patient experience infusion-related adverse effects or hematologic and hepatic toxicity; a moderate renal failure occurred in only one patient.