Ocular Pharmacokinetics of Fluocinolone Acetonide After Retisert™ Intravitreal Implantation in Rabbits Over a 1-Year Period

Driot, Jean-Yves; Novack, Gary D.; Rittenhouse, Kay D.; Milazzo, C.; Pearson, Andrew

doi:10.1089/1080768041223611

Cited by 94 publications

(48 citation statements)

References 9 publications

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“…10 The fluocinolone acetonide intravitreal implant (Retisert; Bausch & Lomb, Bridgewater, NJ) enables sustained corticosteroid release over approximately 3 years into the vitreous cavity. 11 It is approved for intraocular inflammation control in chronic, noninfectious intermediate, posterior, and panuveitis. 12,13 However, its use has been associated with corticosteroid-induced elevation of IOP in 75% of patients, with at least 37%-40% requiring surgery.…”

Section: Introductionmentioning

confidence: 99%

A retrospective study on the outcomes of Ahmed valve versus Ahmed valve combined with fluocinolone implant in uveitic glaucoma

et al. 2017

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Purpose-To compare the intraocular pressure (IOP) outcomes of Ahmed glaucoma valve (AGV) surgery alone versus AGV with fluocinolone implant in uveitic glaucoma patients.Methods-We identified uveitic glaucoma patients with AGV surgery alone and AGV surgery combined with fluocinolone implant from the Massachusetts Eye and Ear Ocular Inflammation Database. Demographic information, visual acuity, and IOP were recorded at preoperative visits and 1, 6, and 12 months after surgery. Incidence of hypertensive phase, defined as an IOP of >21 mm Hg or use of additional treatment to lower IOP occurring any time between 7 days to 6 months postoperatively, was investigated. Multilevel mixed effects models were performed to compare the outcomes between groups.Results-Eighteen eyes of 13 uveitic glaucoma patients with 1-year follow-up data were included. There were 11 eyes of 9 patients (mean age, 56.5 years; 63.6% male) in the AGV group and 7 eyes of 4 patients (mean age, 61.3 years; 71.4% male) in the AGV + fluocinolone group. There was no significant difference in visual acuity change at 1 year after surgery between groups (P = 0.25), although visual acuity improvement was significant in the AGV group (P = 0.01). The hypertensive phase occurred in 91% of AGV patients and 43% of AGV + fluocinolone patients (P = 0.30), with onset of 8-40 days (mean, 18 days) after surgery. IOP and number of glaucoma medications decreased at the 1-year postoperative visits in both the AGV group (P < 0.0001, P < 0.0001) and the AGV + fluocinolone group (P = 0.001, P < 0.0001). Compared to the AGV group, the AGV + fluocinolone group used fewer glaucoma medications (0.28 vs 1.30 [P = 0.01]) and had better inflammation control (P = 0.02). The surgical complication rates were similar between groups.Conclusions-In uveitic glaucoma, AGV with fluocinolone achieves a similar, desired IOP control but with fewer glaucoma medications than AGV alone.

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Section: Introductionmentioning

confidence: 99%

A retrospective study on the outcomes of Ahmed valve versus Ahmed valve combined with fluocinolone implant in uveitic glaucoma

et al. 2017

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“…4 This study utilized the same rabbit species, analytical method, and analytical laboratory as the current study. The levels in C/RPE and I/CB with the Retisert implant were approximately twice those observed with the Iluvien implant.…”

Section: Discussionmentioning

confidence: 99%

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

Kane¹,

Green

2015

Journal of Ocular Pharmacology and Therapeutics

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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.

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“…The MRT of the drug clearly demonstrated that ODE-cCDV stayed in retina and choroid much longer than in vitreous. Compared to the surgical intravitreal implant, which is designed to have zeroorder kinetics and can produce consistent drug levels in retina during the most of its release course, 17 this crystalline drug delivery system produced a less consistent drug level in retina. Nonetheless, this delivery system produced a 2 to 3 weeks of constant drug level in retina and choroid, which is 33% of the total release period.…”

Section: Discussionmentioning

confidence: 99%

Intraocular Pharmacokinetics of a Crystalline Lipid Prodrug, Octadecyloxyethyl-Cyclic-Cidofovir, for Cytomegalovirus Retinitis

Cheng

Beadle

Tammewar

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To evaluate the intraocular pharmacokinetics of octadecyloxyethyl-cyclic-cidofovir (ODE-cCDV) after intravitreal injection into rabbit eyes. Methods: Twenty-seven New Zealand red rabbits (27 eyes) received intravitreal injections of 14 C-labeled ODEcCDV (100 mg drug suspended in 5% dextrose), and ocular tissues were collected from 3 rabbits at each predetermined time point (1 h, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 5 weeks, and 9 weeks) after the injection. The eye globes were enucleated, and the vitreous, retina, and choroids were separated and harvested into preweighed scintillation vials. Levels of ODE-cCDV were measured by counting in a liquid scintillation counter, and pharmacokinetic (PK) parameters were determined. In addition, 3 eyes of 3 animals were used for autoradiography study at day 1, week 3, and week 6. Results: ODE-cCDV in vitreous as a whole followed a 2-phase first-order elimination, whereas ODE-cCDV in retina and choroid manifested a nearly steady state during the first 3 weeks and then followed a first-order elimination with the apparent elimination half-life of 10.1 and 7.2 days. For vitreous, apparent elimination halflife was 25 days. However, the drug mean residence time was much longer in retina (17.6 days) and choroid (19.6 days) than that in the vitreous (11.6 days). The drug exposure to the retina [area under the curve (AUC) ¼ 1120837.1 ng Á day/mL] was greater than the exposure to the vitreous (AUC ¼ 958645.8 ng Á day/mL) and the choroid (AUC ¼ 415407.47). Conclusion: A crystalline lipid prodrug, ODE-cCDV, has longer vitreous half-life than that in other ocular tissues due to its solid drug depot formation in vitreous. Over time, dissolved free ODE-cCDV from drug depot feeds and accumulates in the retina.

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Ocular Pharmacokinetics of Fluocinolone Acetonide After Retisert™ Intravitreal Implantation in Rabbits Over a 1-Year Period

Abstract: In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility.

Cited by 94 publications

References 9 publications

A retrospective study on the outcomes of Ahmed valve versus Ahmed valve combined with fluocinolone implant in uveitic glaucoma

A retrospective study on the outcomes of Ahmed valve versus Ahmed valve combined with fluocinolone implant in uveitic glaucoma

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

Intraocular Pharmacokinetics of a Crystalline Lipid Prodrug, Octadecyloxyethyl-Cyclic-Cidofovir, for Cytomegalovirus Retinitis

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