indication

For the treatment of inflammation and pain associated with ocular surgery.

pharmacology

Difluprednate is a corticosteroid used as an anti-inflammatory steroidal drug used primarily in ocular surgery.

mechanism of action

Corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins (lipocortins). It is postulated that these proteins control the biosynthesis of potent mediators of infammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

toxicity

Preclinical pharmacokinetic and toxicity studies have established that difluprednate ophthalmic emulsion 0.05% given 4 times a day is not toxic to the eye.

biotransformation

Difluprednate is rapidly deacetylated in the aqueous humor to difluoroprednisolone butyrate (DFB), the drug’s active metabolite. Endogenous tissue esterases then metabolize DFB to the inert metabolite hydroxyfluoroprednisolone butyrate (HFB), which limits systemic exposure to the active compound.

absorption

Difluprednate penetrates the corneal epithelium rapidly and effectively. The systemic absorption of difuprednate after ocular instillation of difluprednate is limited.

route of elimination

78.5% of radioactivity was excreted aftert 24 hours, and 99.5% by 7 days after a single dose of labeled difluprednate instilled in the right eyes of pigmented rabbits.