Fluocinolone acetonide (FAc): Pharmacokinetics and clinical relevance.

Abstract

Purpose : FAc intravitreal implant (ILUVIEN^®) is the only approved therapy for diabetic macular edema (DME) that continuously releases drug for 36 months. Pharmacokinetic analyses have shown that the FAc implant releases a submicrogram (0.2 µg/day) dose of fluocinolone acetonide, providing steady-state human aqueous concentrations of approximately 1 ng/mL. This 3-year duration of release, with near-zero order kinetic profile, is currently possible only with non-bioerodable technology. There is little pharmacokinetic evidence to educate clinicians on the appropriate transition between intravitreally or topically administered steroids and an FAc implant. This study assessed available data for FAc implant pharmacokinetics and evaluated possible distinctions from other intravitreal steroid dosage forms.

Methods : A PubMed database search was conducted for studies between 01/01/2006 and 17/11/2016. Search terms were ‘intravitreal AND steroids AND pharmacokinetics’. Seventy-eight studies were identified and screened for likely relevance for a DME indication. The exclusion criteria included review papers, clinically non-relevant dosages, or those studies addressing new, investigative formulations/drug-delivery systems. This resulted in 8 studies of interest being included in the analysis.

Results : Analysis of publications with animal PK models showed that the FAc implant releases ~1.0 ng/mL of steroid from first day post-implant, which is vastly different over time when compared with dexamethasone implant (1x10⁶–1x10⁵ ng/mL in first 2 months; ~0.1– 0.001 ng/mL in steady-state up to 180 days) and triamcinolone injection (~1x10⁷–1x10⁶ng/mL Day 1–120). Despite variability in vitreous concentrations, duration of action in these animal PK models, and lack of comparative human ocular PK studies, all identified studies demonstrated trends in support of low steroid levels with FAc implant compared with alternatives.

Conclusions : Limited data exist regarding the PK of intravitreal steroids. A significant clinical effect has been demonstrated with the FAc implant, which releases a dose that is many orders of magnitude lower than other intravitreal steroids. Knowledge of the relative PK of intravitreal steroids allows for a more informed clinical decision regarding initial steroid therapy and when changing to alternative steroid therapy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.