CLINICAL AND PHARMACOKINETIC EVALUATION OF A NEW LIPID-BASED DELIVERYSYSTEM OF AMPHOTERICIN-B IN AIDS PATIENTS

To evaluate the safety, tolerance and pharmacokinetics of a new formul ation of amphotericin B (AmB; CAS 1397-89-3) 18 AIDS patients treated for different kinds of mycoses were studied: oropharingeal and/or esop hageal azole-resistant candidiasis (9), CNS cryptococcosis (7) or aspe rgillosis (2). Amphotericin B daily dose was infused in 100 ml of a li pid emulsion. The patients aged from 26 to 54 years with body weight r anging from 42 to 89 kg. Blood samples were collected at fixed interva ls and plasma stored at -20 degrees C until tested by a specific HPLC assay. The individual kinetic analysis of plasma drug levels was perfo rmed by a two-compartment open model. The data were analyzed using P-P harm, a computer program designed for population pharmacokinetic analy sis that allows pooling of data. The effect of a variety of demographi c factors on clearance and volume of distribution was investigated. Th e 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 i nterindividual 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 t olerance was very good and no patient experienced infusion-related adv erse effects or hematologic and hepatic toxicity; a moderate renal fai lure occurred in only one patient.