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.
Villani
P
P
Pharmacology Department, S. Matteo Hospital, Pavia, Italy.
Regazzi
M B
MB
Maserati
R
R
Viale
P
P
Alberici
F
F
Giacchino
R
R
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism*; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008055:Lipids; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000378:metabolism
D000935:Antifungal Agents; D008055:Lipids; D000666:Amphotericin B