Abstract
Abstract: :
Purpose: The present study was designed to examine the pharmacokinetics and toxicology of a fluocinolone acetonide (FA) intravitreal implant in pigmented rabbits. Methods: a) Pharmacokinetics: Pigmented rabbits were randomly assigned to receive either a 0.5 mg or 2.0 mg FA intravitreal implant (RetisertTM). Four animals were sacrificed per time point (2 hours, 2 weeks, and 3, 6, 9 and 12 months after implantation) for FA intraocular levels determination. b) Toxicology: Groups of pigmented rabbits received 0.5 mg, 2 mg and 6 mg FA or sham implants, were followed for 6 or 12 months, and sacrificed for histopathology. Results:a) In the vitreous, concentration of FA was relatively constant from the first time point, 2 hours, through 1 year, and dose–related, approximately 7 to 8–fold greater in the 2 mg implant. Concentrations of FA were generally higher in the vitreous (11–18 and 75–146 ng/g) and retina (42–87 and 224–489 ng/g) than in the aqueous humor (0.21–1.1 and 2.6–13.0 ng/mL) for the 0.5 and 2 mg implants, respectively. Urine and plasma values were below the lower limit of quantitation (200 pg/mL) for all observations, indicating no evidence of systemic absorption. b) Implants containing up to 6 mg FA were well tolerated during the one year observation period after implantation. There were no FA related ocular or systemic toxic effects. Conclusion: In this rabbit study, the RetisertTM provided relatively constant levels of FA in the posterior pole, an acceptable safety profile, which is consistent with previous reports of its clinical utility.
Keywords: uveitis–clinical/animal model • pharmacology • retina