Effects of lipid-based oral formulations on plasma and tissue amphotericin B concentrations and renal toxicity in male rats.
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.
D000284:Administration, Oral; D000666:Amphotericin B / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D003840:Deoxycholic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007674:Kidney Diseases / Q000139:chemically induced*; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008823:Micelles; D010710:Phosphates / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014280:Triglycerides / Q000737:chemistry / Q000493:pharmacokinetics
D000935:Antifungal Agents; D008055:Lipids; D008823:Micelles; D010710:Phosphates; D014280:Triglycerides; D003840:Deoxycholic Acid; D000666:Amphotericin B; D003404:Creatinine; C018279:sodium phosphate