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Echevarría, I. et al.

Comparative pharmacokinetics, tissue distributions, and effects on renal function of novel polymeric formulations of amphotericin B and amphotericin B-deoxycholate in rats.

The pharmacokinetic profiles of a traditional formulation of amphotericin B (Fungizone) and novel nanosphere and mixed micelle delivery systems developed for amphotericin B were compared and described. Six groups of male Wistar rats received intravenous injections of the different formulations. Plasma and tissue samples were obtained at 11 different times after dosing, with three animals used each time. The amphotericin B concentrations in plasma and tissues were analyzed by high-performance liquid chromatography. The plasma drug concentration-time profiles were best described by a two-compartment model. Models that described the observed single or double peak disposition kinetics in kidney, liver, and spleen were also developed. Parameter estimates from those models show that components of the formulation such as poloxamer 188, which is present in all new formulations, seem to play an important role in the rate of drug uptake by the tissues; in general, the levels of amphotericin B in tissues were increased after the administration of the new formulations compared with those after the administration of Fungizone. The increment in the baseline plasma creatinine level was used as an index of renal function. All formulations increased this baseline value, but the novel formulations exhibited fewer renal effects than Fungizone did. However, a direct relationship between drug exposure in the kidneys and development of renal damage could not be found.[1]

References

Comparative pharmacokinetics, tissue distributions, and effects on renal function of novel polymeric formulations of amphotericin B and amphotericin B-deoxycholate in rats. Echevarría, I., Barturen, C., Renedo, M.J., Trocóniz, I.F., Dios-Viéitez, M.C. Antimicrob. Agents Chemother. (2000) [Pubmed]

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