TY - JOUR
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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U2 - 10.1167/iovs.02-1020
DO - 10.1167/iovs.02-1020
M3 - Article
C2 - 12714650
AN - SCOPUS:0037406802
SN - 0146-0404
VL - 44
SP - 2112
EP - 2117
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 5
ER -