Nepafenac

Absorption

Nepafenac rapidly cross the cornea (6 times faster than diclofenac in vitro).

Toxicity

Ocularly applied non-steroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

Description

Nepafenac, launched by Alcon Laboratories, is a topical ophthalmic medication indicated for the treatment of ocular pain and inflammation associated with cataract surgery. Nepafenac is a prodrug of amfenac, which is an NSAID and a potent non-selective inhibitor of COX-1 (IC50=0.25 μM)) and COX-2 (IC50=0.15μM). Nepefenac itself exhibits only weak activity against COX-1 (IC50=64.3μM). Amfenac (Fenazox) has been marketed in Japan since 1986 for the treatment of rheumatoid arthritis, post-surgical pain, and inflammation. With most NSAIDs that are currently being used as topical ophthalmic agents, the maximum drug concentration is achieved on the ocular surface, with progressively lower concentrations in the cornea, aqueous humor, vitreous, and retina. Nepafenac has been found to have a penetration coefficient that is 4-28 times greater than that achieved with conventional NSAIDs such as diclofenac, bromofenac, and ketorolac. In addition, the bioconversion of nepefenac to amfenac is primarily mediated by ocular tissue hydrolases, specifically in the iris, ciliary body, retina, and choroid. The enhanced permeability of nepefenac combined with rapid bioactivation in the ocular tissue translates into superior anti-inflammatory efficacy at the target sites.

The Uses of Nepafenac

Nepafenac is a non-steroidal anti-inflammatory drug (NSAID), usually sold as a prescription eye drop. It reduces pain and inflammation in the eyes. Nepafenac ophthalmic is used to reduce pain and swelling after cataract surgery.

What are the applications of Application

Nepafenac is an analgesic selective inhibitor of COX-2

Background

Nepafenac is a non-steroidal anti-inflammatory prodrug (NSAID) usually sold as a prescription eye drop. It is used to treat pain and inflammation associated with cataract surgery.

Indications

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

Pharmacokinetics

Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular TID dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration.

Metabolism

Nepafenac (prodrug) is deaminated to amfenac (active compound) in the ciliary body epithelium, retina, and choroid by intraocular hydrolases. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.