Epinastine

Epinastine is a topically active, direct H₁-receptor antagonist. Epinastine has a high binding affinity for the histamine H₁-receptor and a 400 times lower affinity for the histamine H₂receptor. Epinastine also possesses affinity for the a₁, a₂-, and the 5-HT₂–receptor. It has low affinity for cholinergic, dopaminergic and a variety of other receptor sites. Epinastine does not penetrate the blood/brain barrier and, therefore, does not induce side effects of the central nervous system, i.e., it is non-sedative.

Pharmacodynamic effects

Following topical eye application in animals, epinastine showed evidence for antihistaminic activity, a modulating effect on the accumulation of inflammatory cells, and mast cell stabilising activity.

In provocation studies with allergens in humans, epinastine was able to ameliorate ocular symptoms following ocular antigen challenge. The duration of the effect was at least 8 hours.

Absorption

Following administration of one drop of epinastine in each eye twice daily, an average maximum plasma concentration of 0.042 ng/ml is reached after about two hours.

Distribution

Epinastine has a volume of distribution of 417 litres and is 64% bound to plasma proteins.

Biotransformation

Less than 10% is metabolised.

Elimination

The clearance is 928 ml/min and the terminal plasma elimination half-life is about 8 hours.

Epinastine is mainly excreted renally unchanged. The renal elimination is mainly via active tubular secretion.

Preclinical studies in vitro and in vivo show that epinastine binds to melanin and accumulates in the pigmented ocular tissues of rabbits and monkeys. In vitro data indicate that the binding to melanin is moderate and reversible.

Non clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential toxicity to reproduction and development.