Intravitreal ceftriaxone in a rabbit model. Dose- and time-dependent toxic effects and pharmacokinetic analysis

Ceftriaxone's toxic effects were assessed in albino rabbits after intravitreal injection. Doses up to 5 mg did not alter the B-wave amplitude. Following 7.5-and 20-mg doses, B-wave amplitude ratios were depressed at 24 hours and normal at seven and 14 days. A 50-mg dose caused a temporarily flat B-wave 24 hours after injection. At two weeks this ratio exhibited a moderate increase but remained 2 SDs below the mean preinjection ratio. Eyes receiving up to 20 mg were normal histologically at 14 days. A 50-mg dose induced generalized retinal edema and disruption of the retinal layers 24 hours after injection; at two weeks there were no histologic changes in the retina. Immediately after a 2-mg intravitreal injection, vitreous ceftriaxone levels were 1,345 +/- 4.9 mg/L; by 72 hours they had decreased to 17.6 +/- 1.4 mg/L. The mean peak aqueous level was 80.2 +/- 12.2 mg/L at 72 hours.