Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model

Invest Ophthalmol Vis Sci. 2003 May;44(5):2112-7. doi: 10.1167/iovs.02-1020.

Abstract

Purpose: To determine the toxicity of various doses of intravitreal amphotericin B deoxycholate, amphotericin B lipid complex (ABLC), and liposomal amphotericin B (L-AmB).

Methods: Fifty-two rabbits were divided into two treatment groups (groups A and B). Thirteen treatments were administered intravitreally to the 104 rabbit eyes. Treatments included a control plus 10, 20, 30, and 50 micro g amphotericin B deoxycholate, ABLC, and L-AmB. Eye examinations were performed before injection and on day 11 for group A and on day 18 for group B. At death, on days 13 and 21 in groups A and B, respectively, vitreous humor was aspirated and concentrations of amphotericin B were determined by high performance liquid chromatography (HPLC), followed by enucleation for histologic studies.

Results: Significantly more eyes treated with ABLC showed development of vitreal opacities than developed in eyes treated with amphotericin B deoxycholate or L-AmB (P < 0.05). Vitreal band formation was significantly higher in ABLC-treated eyes than in those treated with L-AmB, (P = 0.039). Vitreal inflammation was greater in eyes treated with L-AmB (75%), amphotericin B deoxycholate (78%), and ABLC (91%) than with the control (50%; P = 0.08). Retinal ganglion cell loss was greater in eyes treated with amphotericin B deoxycholate (81%), L-AmB (91%), and ABLC (97%) than with the control (38%; P = 0.003). Amphotericin B concentrations were measurable for all doses of the three formulations.

Conclusions: Based on histologic data, increasing doses of all three agents appear to be associated with increasing toxicity, however based on ophthalmologic data, L-AmB appears to be less toxic than either amphotericin B deoxycholate or ABLC.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / pharmacokinetics
  • Amphotericin B / toxicity*
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / toxicity*
  • Chromatography, High Pressure Liquid
  • Deoxycholic Acid / administration & dosage
  • Deoxycholic Acid / analogs & derivatives*
  • Deoxycholic Acid / pharmacokinetics
  • Deoxycholic Acid / toxicity*
  • Drug Combinations
  • Eye Diseases / chemically induced*
  • Eye Diseases / pathology
  • Phosphatidylcholines / administration & dosage
  • Phosphatidylcholines / pharmacokinetics
  • Phosphatidylcholines / toxicity*
  • Phosphatidylglycerols / administration & dosage
  • Phosphatidylglycerols / pharmacokinetics
  • Phosphatidylglycerols / toxicity*
  • Rabbits
  • Retinal Diseases / chemically induced
  • Retinal Ganglion Cells / drug effects
  • Vitreous Body / drug effects*
  • Vitreous Body / metabolism
  • Vitreous Body / pathology

Substances

  • Antifungal Agents
  • Drug Combinations
  • Phosphatidylcholines
  • Phosphatidylglycerols
  • liposomal amphotericin B
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination