Toxicity and pharmacokinetics of subconjunctival amphotericin B. An experimental study.
The pharmacokinetics and toxicity of subconjunctival (S/C) amphotericin B (AmB) were evaluated in Dutch-belted rabbits. Following the S/C injection of 1,500 micrograms of AmB, corneal and aqueous levels were determined by bioassay. The highest levels were present in the periphery of debrided corneas at 1 h (90.12 +/- 2.4 micrograms/g). The debrided central cornea contained 30.84 micrograms/g, almost double the amount present in the intact central cornea. These levels were transient; in the central intact cornea only 2.08 micrograms/g could be detected at 2 h. Peak aqueous levels were low (0.95 +/- .24 micrograms/mL in debrided corneas at 1 h). The S/C injection of 1,500 micrograms of AmB in sodium deoxycholate produced a severe inflammatory response in the conjunctiva, episclera, iris, anterior chamber, and superior rectus muscle that persisted 10 days. Injection of sodium deoxycholate alone produced a similar but less severe response.
Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee.
D M
DM
O'Day
R
R
Smith
J B
JB
Stevens
T E
TE
Williams
R D
RD
Robinson
W S
WS
Head
D000666:Amphotericin B / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism / Q000473:pathology; D001082:Aqueous Humor / Q000378:metabolism; D003228:Conjunctiva; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003840:Deoxycholic Acid / Q000008:administration & dosage; D005123:Eye / Q000378:metabolism* / Q000473:pathology; D009801:Oculomotor Muscles / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D014018:Tissue Distribution
D003840:Deoxycholic Acid; D000666:Amphotericin B