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Antimicrobial Agents and Chemotherapy, April 2000, p. 898-904, Vol. 44, No. 4
Department of Pharmacy and Pharmaceutical
Technology, Faculty of Pharmacy, University of Navarra, 31080, Pamplona, Spain
Received 19 April 1999/Returned for modification 16 October
1999/Accepted 14 January 2000
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.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Comparative Pharmacokinetics, Tissue Distributions, and
Effects on Renal Function of Novel Polymeric Formulations of
Amphotericin B and Amphotericin B-Deoxycholate in Rats
*
Corresponding author. Mailing address: Departamento de
Farmacia y Tecnología Farmacéutica, Facultad de Farmacia,
Universidad de Navarra, 31080 Pamplona, Spain. Phone: 34 948 425600, ext. 6375 or 6442. Fax: 34 948 425649. E-mail:
mcdios{at}unav.es.
Antimicrobial Agents and Chemotherapy, April 2000, p. 898-904, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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