Pharmacokinetics, tissue distribution, and toxicity of free and liposomal amphotericin B in diabetic rats

The Journal of Infectious Diseases
K M WasanD R Luke

Abstract

The pharmacokinetics, tissue distribution, and toxicity of free amphotericin B (free AmB) or amphotericin B encapsulated in liposomes (L-AmB) were characterized in experimental diabetic rats and compared with data obtained from nondiabetic rats. After 7 days of insulin-controlled diabetes or saline, each rat was administered a single intravenous bolus dose of free AmB or L-AmB (0.8 mg/kg body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, nephrotoxicity, and biochemical parameters. Before drug treatment, diabetic rats demonstrated marked increases in serum cholesterol and triglyceride levels compared with levels in nondiabetic rats. A significant increase in serum creatinine levels was observed in nondiabetic rats given free AmB but not in other groups. Whereas AmB pharmacokinetics were significantly altered in diabetic rats administered free AmB, no kinetic differences were found between groups given L-AmB. Renal AmB levels were markedly increased in nondiabetic rats given free AmB compared with those in all other groups. Furthermore, significantly greater concentrations of free AmB were found in lung tissue of rats administered L-AmB independent...Continue Reading

Citations

Jan 1, 1997·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·K M Wasan, G Lopez-Berestein
Jun 1, 1994·Journal of Pharmaceutical and Biomedical Analysis·K M WasanG Lopez-Berestein
Mar 29, 2001·Journal of Pharmaceutical and Biomedical Analysis·T Eldem, N Arican-Cellat
Dec 14, 2002·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Ric M ProcyshynKishor M Wasan
Jun 3, 1999·British Journal of Haematology·A Clark, I M Franklin
Feb 1, 1993·Antimicrobial Agents and Chemotherapy·K M WasanG Lopez-Berestein
May 1, 1994·Antimicrobial Agents and Chemotherapy·P ChavanetP Yeni
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·A H GrollT J Walsh
Dec 25, 2003·Antimicrobial Agents and Chemotherapy·Karen BartlettKishor M Wasan
Nov 25, 2005·Drug Development and Industrial Pharmacy·Ric M ProcyshynKishor M Wasan
Oct 20, 2004·Drug Development and Industrial Pharmacy·Verica RisovicKishor M Wasan
Jan 1, 1994·Journal of Drug Targeting·K M Wasan, G Lopez-Berestein
Apr 21, 1998·Journal of Pharmaceutical Sciences·K M Wasan, S M Cassidy
Aug 15, 1994·Annals of the New York Academy of Sciences·K M Wasan, G Lopez-Berestein
Jul 25, 2000·Journal of Pharmaceutical Sciences·W N Charman
Jan 24, 2002·Current Opinion in Critical Care·S Costa, M Nucci
Feb 24, 2001·The Annals of Pharmacotherapy·R E QuilitzUNKNOWN H Lee Moffit Cancer Center, Tampa, FL
Nov 7, 1998·Anesthesia and Analgesia·M K ZamaconaR Calvo
Jun 3, 1999·British Journal of Haematology·J Mehta
Feb 4, 1998·Antimicrobial Agents and Chemotherapy·T OtsuboS Kohno
Sep 26, 1997·Antimicrobial Agents and Chemotherapy·K M WasanR L Thies

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