Intravitreal ceftazidime in a rabbit model: dose- and time-dependent toxicity and pharmacokinetic analysis.
We delineated the dose-and time-dependent retinal toxicity of intravitreal ceftazidime using electroretinography (ERG) in phakic rabbit eyes. Toxicity was evaluated following intravitreal doses ranging from 0.5 to 50 mg/0.1 ml. Eyes were examined prior to injection, at one day, and at seven days after injection. ERG patterns at one and seven days indicated a toxic response to doses of 20 to 50 mg. Doses of 10 mg or less gave a transient depression of the B-wave at one day, but a return to normal was observed at the seven-day evaluation. Pharmacokinetic analysis following intravitreal injection of 2 mg of ceftazidime into uninfected phakic rabbit eyes disclosed vitreous levels of: 1711 micrograms/ml at 0 hr; 1340 micrograms/ml at 8 hr; 451 micrograms/ml at 24 hr; 270 micrograms/ml at 48 hr and 67 micrograms/ml at 72 hr. Peak aqueous humor level was 139 micrograms/ml 8 hr post-injection. Potentially therapeutic drug levels were obtained in the aqueous and vitreous humors following a nontoxic intravitreal dose of ceftazidime in a rabbit model.
Jay
W M
WM
Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock.
Fishman
P
P
Aziz
M
M
Shockley
R K
RK
D000818:Animals; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D007267:Injections; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014822:Vitreous Body / Q000378:metabolism
D002442:Ceftazidime