P. Villani et al., CLINICAL AND PHARMACOKINETIC EVALUATION OF A NEW LIPID-BASED DELIVERYSYSTEM OF AMPHOTERICIN-B IN AIDS PATIENTS, Arzneimittel-Forschung, 46(4), 1996, pp. 445-449
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.