Fluocinolone Other names: Fluocinolone acetonide

Fluocinolone acetonide is a synthetic fluorinated corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictive properties. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids.

Corticosteroids inhibit the inflammatory response to a variety of inciting agents. They inhibit the oedema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.

Corticosteroids are thought to act by the induction of phospholipase A inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Corticosteroids have also been shown to reduce levels of vascular endothelial growth factor, a protein which increases vascular permeability and causes oedema.

In a human pharmacokinetic study (C-01-06-002, the FAMOUS Study) fluocinolone acetonide concentrations in plasma were below the lower limit of quantitation of the assay (100 pg/mL) at all time points from Day 1 through Month 36. The maximal aqueous humor fluocinolone acetonide concentrations were observed on Day 7 for most of the subjects. Aqueous humor fluocinolone acetonide concentrations decreased over the first 3−6 months and remained essentially the same through Month 36 for subjects who were not retreated. Subjects who were retreated experienced a second fluocinolone acetonide peak concentration similar to that following the initial dose. After retreatment, aqueous humor concentrations of fluocinolone acetonide returned to levels approximately similar to those observed at the time of first treatment.

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Occlusion of topical corticosteroids can enhance penetration. Topical corticosteroids can be absorbed from normal intact skin. Also, inflammation and/or other disease processes in the skin can increase percutaneous absorption.

Fluocinolone acetonide has been shown to be teratogenic in mice and rabbits following systemic administration. No mutagenicity, carcinogenicity or developmental toxicity data are available for intravitreally administered fluocinolone acetonide. However, intravitreally administered fluocinolone acetonide was not detectable systemically and thus no systemic effects are anticipated.

Local effects (focal degenerative lesions affecting fibers in the posterior polar and posterior cortical regions of the lens) were observed in rabbits at doses of intravitreal fluocinolone acetonide in excess of the clinically used dose. Local effects (focal retinal scarring) were also seen in rabbits treated with both placebo and fluocinolone acetonide containing device. This scarring was not seen clinically in humans and is postulated to be due to anatomical differences between the rabbit and human eye.