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Plasma Protein Binding of Amphotericin B and Pharmacokinetics of Bound versus Unbound Amphotericin B after Administration of Intravenous Liposomal Amphotericin B (AmBisome) and Amphotericin B Deoxycholate
- Source :
- Antimicrobial Agents and Chemotherapy. 46:834-840
- Publication Year :
- 2002
- Publisher :
- American Society for Microbiology, 2002.
-
Abstract
- Unilamellar liposomal amphotericin B (AmBisome) (liposomal AMB) reduces the toxicity of this antifungal drug. The unique composition of liposomal AMB stabilizes the liposomes, producing higher sustained drug levels in plasma and reducing renal and hepatic excretion. When liposomes release their drug payload, unbound, protein-bound, and liposomal drug pools may exist simultaneously in the body. To determine the amounts of drug in these pools, we developed a procedure to measure unbound AMB in human plasma by ultrafiltration and then used it to characterize AMB binding in vitro and to assess the pharmacokinetics of nonliposomal pools of AMB in a phase IV study of liposomal AMB and AMB deoxycholate in healthy subjects. We confirmed that AMB is highly bound (>95%) in human plasma and showed that both human serum albumin and α 1 -acid glycoprotein contribute to this binding. AMB binding exhibited an unusual concentration dependence in plasma: the percentage of bound drug increased as the AMB concentration increased. This was attributed to the low solubility of AMB in plasma, which limits the unbound drug concentration to −1 kg −1 ) for both formulations. Unbound drug urinary clearances were equal to the glomerular filtration rate, and tubular transit rates were
- Subjects :
- Antifungal Agents
animal diseases
Antifungal drug
Ultrafiltration
Pharmacology
Dosage form
Feces
Pharmacokinetics
Amphotericin B
Amphotericin B deoxycholate
parasitic diseases
Blood plasma
medicine
Humans
Pharmacology (medical)
Liposome
Chromatography
urogenital system
Chemistry
technology, industry, and agriculture
Blood Proteins
bacterial infections and mycoses
Drug Combinations
Infectious Diseases
Area Under Curve
Injections, Intravenous
Liposomes
Drug carrier
Dialysis
Deoxycholic Acid
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....d777d5a26eabcd3d6d4055a580edede5