Abstract
The purpose of this study was to determine the effects of various lipid and mixed-micelle formulations on the oral absorption and renal toxicity of amphotericin B (AMB) in rats. The maximum concentration of AMB in plasma and the area under the concentration-time curve for 0 to 24 h for AMB were elevated in rats administered triglyceride (TG)-rich AMB formulations in comparison to those in rats given (i) AMB preformulated as a micelle containing sodium deoxycholate with sodium phosphate as a buffer (DOC-AMB), (ii) an AMB-lipid complex suspension, or (iii) AMB solubilized in methanol. Furthermore, our findings suggest that AMB incorporated into TG-based oral formulations has less renal toxicity than DOC-AMB.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Amphotericin B / blood
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Amphotericin B / chemistry
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Amphotericin B / pharmacokinetics*
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Amphotericin B / toxicity*
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Animals
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Antifungal Agents / blood
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacokinetics
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Antifungal Agents / toxicity
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Area Under Curve
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Creatinine / blood
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Deoxycholic Acid / chemistry
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Deoxycholic Acid / pharmacokinetics
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Drug Delivery Systems
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Kidney Diseases / chemically induced*
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Lipids / chemistry
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Lipids / pharmacokinetics*
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Male
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Micelles
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Phosphates / chemistry
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Phosphates / pharmacokinetics
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Rats
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Rats, Sprague-Dawley
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Tissue Distribution
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Triglycerides / chemistry
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Triglycerides / pharmacokinetics
Substances
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Antifungal Agents
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Lipids
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Micelles
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Phosphates
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Triglycerides
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Deoxycholic Acid
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Amphotericin B
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Creatinine
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sodium phosphate