Comparative Drug Disposition, Urinary Pharmacokinetics, and Renal Effects of Multilamellar Liposomal Nystatin and Amphotericin B Deoxycholate in Rabbits

Andreas H. Groll, Diana Mickiene, Vidmantas Petraitis, Ruta Petraitiene, Raul M. Alfaro, Christine King, Stephen C. Piscitelli, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

The comparative drug dispositions, urinary pharmacokinetics, and effects on renal function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were determined by high-performance liquid chromatography as total concentrations of LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in escalating maximum concentrations (Cmax) (17 to 56 μg/ml for LNYS versus 3.36 μg/ml for DAMB; P <0.001) and values for the area under the concentration-time curve from 0 to 24 h (AUC0-24) (17 to 77 μg · h/ml for LNYS versus 12 μg. · h/ml for DAMB; P <0.001) in plasma but a significantly faster total clearance from plasma (0.117 to 0.080 liter/h/kg for LNYS versus 0.055 liter/h/kg for DAMB; P = 0.013) and a ≤8-fold-smaller volume of distribution at steady state (P = 0.002). Urinary drug concentration data revealed a ≥10-fold-higher Cmax (16 to 10 μg/ml for LNYS versus 0.96 μg/ml for DAMB; P = 0.015) and a 4- to 7-fold-greater AUC0-24 (63 to 35 μg · h/ml for LNYS versus 8.9 μg/ml DAMB; P = 0.015) following the administration of LNYS, with a dose-dependent decrease in the dose-normalized AUC0-24 in urine (P = 0.001) and a trend toward a dose-dependent decrease in renal clearance. Except for the kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after dosing were severalfold lower than those after administration of DAMB (P,

Original languageEnglish (US)
Pages (from-to)3917-3925
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume47
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Nystatin
Pharmacokinetics
Rabbits
Kidney
Pharmaceutical Preparations
Amphotericin B
Spleen
High Pressure Liquid Chromatography
Body Weight
Urine
Lung
Liver
liposomal amphotericin B
deoxycholate drug combination amphotericin B
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Comparative Drug Disposition, Urinary Pharmacokinetics, and Renal Effects of Multilamellar Liposomal Nystatin and Amphotericin B Deoxycholate in Rabbits. / Groll, Andreas H.; Mickiene, Diana; Petraitis, Vidmantas; Petraitiene, Ruta; Alfaro, Raul M.; King, Christine; Piscitelli, Stephen C.; Walsh, Thomas J.

In: Antimicrobial Agents and Chemotherapy, Vol. 47, No. 12, 12.2003, p. 3917-3925.

Research output: Contribution to journalArticle

Groll, Andreas H. ; Mickiene, Diana ; Petraitis, Vidmantas ; Petraitiene, Ruta ; Alfaro, Raul M. ; King, Christine ; Piscitelli, Stephen C. ; Walsh, Thomas J. / Comparative Drug Disposition, Urinary Pharmacokinetics, and Renal Effects of Multilamellar Liposomal Nystatin and Amphotericin B Deoxycholate in Rabbits. In: Antimicrobial Agents and Chemotherapy. 2003 ; Vol. 47, No. 12. pp. 3917-3925.
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abstract = "The comparative drug dispositions, urinary pharmacokinetics, and effects on renal function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were determined by high-performance liquid chromatography as total concentrations of LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in escalating maximum concentrations (Cmax) (17 to 56 μg/ml for LNYS versus 3.36 μg/ml for DAMB; P <0.001) and values for the area under the concentration-time curve from 0 to 24 h (AUC0-24) (17 to 77 μg · h/ml for LNYS versus 12 μg. · h/ml for DAMB; P <0.001) in plasma but a significantly faster total clearance from plasma (0.117 to 0.080 liter/h/kg for LNYS versus 0.055 liter/h/kg for DAMB; P = 0.013) and a ≤8-fold-smaller volume of distribution at steady state (P = 0.002). Urinary drug concentration data revealed a ≥10-fold-higher Cmax (16 to 10 μg/ml for LNYS versus 0.96 μg/ml for DAMB; P = 0.015) and a 4- to 7-fold-greater AUC0-24 (63 to 35 μg · h/ml for LNYS versus 8.9 μg/ml DAMB; P = 0.015) following the administration of LNYS, with a dose-dependent decrease in the dose-normalized AUC0-24 in urine (P = 0.001) and a trend toward a dose-dependent decrease in renal clearance. Except for the kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after dosing were severalfold lower than those after administration of DAMB (P,",
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AU - Walsh, Thomas J.

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