Behavior of amphotericin B lipid complex in plasma in vitro and in the circulation of rats
| Autor: | Lois E. Bolcsak, Rupinder Bhamra, Christine E. Swenson, Andrew S. Janoff, A Sa'ad |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Antifungal Agents Pharmacology Rats Sprague-Dawley chemistry.chemical_compound Therapeutic index In vivo Amphotericin B Amphotericin B deoxycholate Blood plasma medicine Animals Pharmacology (medical) Chromatography High Pressure Liquid Whole blood Cholesterol Phosphatidylglycerols bacterial infections and mycoses Rats Drug Combinations Infectious Diseases chemistry Immunology Phosphatidylcholines Deoxycholic Acid Research Article Lipoprotein medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 41:886-892 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Amphotericin B lipid complex (ABLC) shows reduced toxicity relative to that of amphotericin B deoxycholate (AmB-d) while maintaining antifungal activity. Rat blood or plasma was spiked with ABLC in vitro. Released amphotericin B was separated from the parent material by centrifugation. At early times (0 to 15 min) most (approximately 90%) of the amphotericin B was complexed. The amount of released amphotericin B increased gradually in a time- and temperature-dependent fashion. The released amphotericin B was associated with plasma lipoprotein and nonlipoprotein proteins. The area under the concentration-time curve from 0 to 24 h for total amphotericin B in whole blood of rats given a single intravenous bolus dose of 1 mg of ABLC per kg of body weight was fourfold lower than that in rats given 1 mg of AmB-d per kg. The complexed amphotericin B was rapidly removed from the circulation and was distributed to the tissues in these rats. Other rats were treated intravenously with ABLC (10 mg/kg/day) or AmB-d (0.5 mg/kg/day) daily for 15 days. Blood was collected at 15 and 180 min after administration of the last dose. The total levels of amphotericin B in the blood of the group given ABLC were about three to five times those in the group given AmB-d, and the concentration of released, protein-bound amphotericin B in the plasma of the group given ABLC was about one to two times that observed for the group given AmB-d, despite the 20-fold difference in dose. The relative protein distribution of amphotericin B in plasma was similar after ABLC or AmB-d administration under these steady-state conditions in vivo. The rapid uptake of complexed amphotericin B by tissues and the very low levels of circulating protein-bound amphotericin B in plasma after the administration of ABLC may explain, in part, the reduced toxicity and enhanced therapeutic index of this preparation. |
| Databáze: | OpenAIRE |
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