Pharmacology Of Azelastine

Indication	For the symptomatic treatment of seasonal allergic rhinitis and non-allergic rhinitis, as well as symptomatic relief of ocular itching associated with allergic conjunctivitis.
Pharmacodynamics	Azelastine is a relatively selective histamine H1 antagonist, which inhibits the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. It has some affinity to H2 receptors. Based on in vitro studies using human cell lines, inhibition of other mediators involved in allergic reactions (e.g. leukotrienes and PAF) has been demonstrated with azelastine. Azelastine may also inhibit the accumulation and degranulation of eosinophils at the site of allergic inflammation.
Mechanism of action	Azelastine competes with histamine for the H1-receptor sites on effector cells and acts as an antagonist by inhibiting the release of histamine and other mediators involved in the allergic response.
Absorption	Absorption of azelastine following ocular administration was relatively low. Systemic bioavailability is approximately 40% after nasal administration.
Volume of distribution	14.5 L/kg
Protein binding	In-vitro studies in human plasma indicate that the plasma protein binding of azelastine and N-desmethylazelastine are approximately 88% and 97%, respectively.
Metabolism	Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system, however the exact cytochrome P450 isoenzyme involved has not been determined. The major metabolite, desmethylazelastine, also has H1-receptor antagonist activity.
Route of elimination	Approximately 75% of an oral dose of radiolabeled azelastine hydrochloride was excreted in the feces with less than 10% as unchanged azelastine. Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system.
Half life	Elimination half-life (based on intravenous and oral administration) is 22 hours. Elimination half-life of the active metabolite, desmethylazelastine, is 54 hours (after oral administration of azelastine).
Clearance	0.5 L/h/kg [symptomatic patients]
Toxicity	Not Available