Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model.
OBJECTIVE
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.
Cannon
Joan P
JP
Department of Pharmacy, Hines VA Hospital, Hines, Illinois, USA.
Fiscella
Richard
R
Pattharachayakul
Sutthiporn
S
Garey
Kevin W
KW
De Alba
Felipe
F
Piscitelli
Stephen
S
Edward
Deepak P
DP
Danziger
Larry H
LH
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity*; D004338:Drug Combinations; D005128:Eye Diseases / Q000139:chemically induced* / Q000473:pathology; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D011817:Rabbits; D012164:Retinal Diseases / Q000139:chemically induced; D012165:Retinal Ganglion Cells / Q000187:drug effects; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination