Clinical and Pharmacokinetic Evaluation of a New Lipid-based Delivery System of Amphotericin B in AIDS Patients

Paola Villani, Mario B. Regazzi, Renato Maserati, Pierluigi Viale, Francesco Alberici, Roberto Giacchino

Research output: Contribution to journalArticle

Abstract

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°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 experienced infusion-related adverse effects or hematologic and hepatic toxicity; a moderate renal failure occurred in only one patient.

Original languageEnglish
Pages (from-to)445-449
Number of pages5
JournalArzneimittel-Forschung/Drug Research
Volume46
Issue number4
Publication statusPublished - 1996

Keywords

  • Amphotericin B, lipid emulsion, pharmacokinetics
  • Antimycotics
  • CAS 1397-89-3
  • Intralipid®

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

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