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

Joan P. Cannon, Richard Fiscella, Sutthiporn Pattharachayakul, Kevin W. Garey, Felipe De Alba, Stephen Piscitelli, Deepak P. Edward, Larry H. Danziger

Research output: Contribution to journalArticle

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 μg 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%), LAmB (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.

Original languageEnglish (US)
Pages (from-to)2112-2117
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

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Amphotericin B
Rabbits
liposomal amphotericin B
Vitreous Body
Retinal Ganglion Cells
Poisons
deoxycholate drug combination amphotericin B
Therapeutics
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Cannon, J. P., Fiscella, R., Pattharachayakul, S., Garey, K. W., De Alba, F., Piscitelli, S., ... Danziger, L. H. (2003). Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model. Investigative Ophthalmology and Visual Science, 44(5), 2112-2117. https://doi.org/10.1167/iovs.02-1020

Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model. / Cannon, Joan P.; Fiscella, Richard; Pattharachayakul, Sutthiporn; Garey, Kevin W.; De Alba, Felipe; Piscitelli, Stephen; Edward, Deepak P.; Danziger, Larry H.

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 5, 01.05.2003, p. 2112-2117.

Research output: Contribution to journalArticle

Cannon, JP, Fiscella, R, Pattharachayakul, S, Garey, KW, De Alba, F, Piscitelli, S, Edward, DP & Danziger, LH 2003, 'Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model', Investigative Ophthalmology and Visual Science, vol. 44, no. 5, pp. 2112-2117. https://doi.org/10.1167/iovs.02-1020
Cannon, Joan P. ; Fiscella, Richard ; Pattharachayakul, Sutthiporn ; Garey, Kevin W. ; De Alba, Felipe ; Piscitelli, Stephen ; Edward, Deepak P. ; Danziger, Larry H. / Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 5. pp. 2112-2117.
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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 μg 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{\%}), LAmB (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.",
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T1 - Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model

AU - Cannon, Joan P.

AU - Fiscella, Richard

AU - Pattharachayakul, Sutthiporn

AU - Garey, Kevin W.

AU - De Alba, Felipe

AU - Piscitelli, Stephen

AU - Edward, Deepak P.

AU - Danziger, Larry H.

PY - 2003/5/1

Y1 - 2003/5/1

N2 - 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 μg 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%), LAmB (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.

AB - 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 μg 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%), LAmB (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.

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