Ocular Pharmacokinetics of Fluocinolone Acetonide Following Iluvien Implantation in the Vitreous Humor of Rabbits

Abstract

Purpose: The purpose of this study was to evaluate the systemic and ocular pharmacokinetics (PK) of fluocinolone acetonide (FAc) following administration of Iluvien Ò intravitreal implants. Methods: The FAc intravitreal implant was administered to rabbits in 3 doses (0.2, 0.5, and 1.0 mg/day). The concentration of FAc was measured by a validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method in plasma and ocular tissues at various time points through month 24. Results: Following administration of the 0.2 mg/day implant, FAc levels peaked in most tissues at day 2 or 8, reached approximate steady state levels by month 3 and very gradually decreased over the duration of the study. The FAc level in the aqueous humor was not measurable at most time points in the rabbit. FAc was still present in most ocular tissues at 2 years. The 0.5 and 1.0 mg/day dose groups followed the same pattern through month 9. The elimination half lives in the tissues for which it was measurable were greater than 83 days. Exposure to FAc was highest in the choroid/retinal pigment epithelium for all doses, followed by lens and retina. Conclusions: The results of this study demonstrate sustained delivery of FAc from the Iluvien intravitreal implant in the ocular tissue of rabbits. Retina and lens FAc levels with the Iluvien implant were approximately 1/10 those reported with the Retisert Ò implant. FAc levels in the aqueous were not measureable with Iluvien where they were measured for 12 months with Retisert.

Intravitreal Corticosteroids in Diabetic Macular Edema

“…Release kinetics of ILUVIEN FAc implants were studied in pigmented rabbits. 34 After intravitreal injection of different doses of FAc implants, exposure in the vitreous humor was assessed (Figure 4 ). Quantifiable FAc concentrations were not observed at any dose level in the plasma (lower limit of quantitation, 100 pg/mL for ILUVIEN).…”

“… Mean (±standard error of the mean) FAc concentration in the vitreous humor of rabbits. 34 Asterisk indicates that a second randomized treatment was administered during Week 52. …”

Clinical utility of intravitreal fluocinolone acetonide (Iluvien^®) implant in the management of patients with chronic diabetic macular edema: a review of the current literature

“…The dose of 190 μg releases the drug at a rate of 0.2 μg per day. The release kinetics of FA implants have been studied in humans and rabbits, and the corticosteroid maximum concentration in the aqueous found with FA implants were found to be several orders of magnitude lower than either triamcinolone or the bioerodible system releasing dexamethasone (Ozurdex ® ; Allergan)25 and also lower than the aqueous maximum concentration level of commonly used corticosteroid eye drops such as Pred Forte 1% (mean C max between 669.9 and 1,130 ng/mL vs 2.17 ng/mL for the FA implant).…”

ILUVIEN—A New Approach to the Treatment of Diabetic Macula Edema

“…After Fluocinolone acetonide was still present in most ocular tissues at 2 years. 28,29 This finding was confirmed in the Fluocinolone Acetonide in Human Aqueous (FAMOUS) study at 36 months. 30 The FAME clinical trials-analyses that supported the US indicationexamined the IOP-lowering surgeries as a function of previous ocular steroid prior to study entry.…”