Molecule

Drug Groups

approved

Description

Azelastine, a phthalazine derivative, is an antihistamine and mast cell stabilizer available as a nasal spray for hay fever and as eye drops for allergic conjunctivitis.

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.

Pharmacology

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.

Affected Organisms

Biotransformation

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.

Absorption

Absorption of azelastine following ocular administration was relatively low. Systemic bioavailability is approximately 40% after nasal administration.

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).

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.

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.

Distribution

* 14.5 L/kg

Clearance

* 0.5 L/h/kg [symptomatic patients]

References

External Links