Optivar Pharmacology, Pharmacokinetics, Studies, Metabolism - Azelastine hydrochloride

Optivar Pharmacology, Pharmacokinetics, Studies, Metabolism - Azelastine hydrochloride

CLINICAL PHARMACOLOGY

Azelastine hydrochloride is a relatively selective histamine H₁ antagonist and an inhibitor of the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. 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 hydrochloride. Decreased chemotaxis and activation of eosinophils has also been demonstrated.

Absorption of azelastine following ocular administration was relatively low. A study in symptomatic patients receiving one drop OPTIVAR™ in each eye two to four times a day (0.06 to 0.12 mg azelastine hydrochloride) demonstrated plasma concentrations of azelastine hydrochloride to generally be between 0.02 and 0.25 ng/mL after 56 days of treatment. Three of nineteen patients had quantifiable amounts of N-desmethylazelastine that ranged from 0.25–0.87 ng/mL at Day 56.

Based on intravenous and oral administration, the elimination half-life, steady-state volume of distribution and plasma clearance were 22 hours, 14.5 L/kg and 0.5 L/h/kg, respectively. 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. In-vitro studies in human plasma indicate that the plasma protein binding of azelastine and N-desmethylazelastine are approximately 88% and 97%, respectively.

In a conjunctival antigen challenge study, OPTIVAR™ was more effective than its vehicle in preventing itching associated with allergic conjunctivitis. OPTIVAR™ had a rapid (within 3 minutes) onset of effect and a duration of effect of approximately 8 hours for the prevention of itching.

In environmental studies, adult and pediatric, patients with seasonal allergic conjunctivitis were treated with OPTIVAR™ for two to eight weeks. In these studies, OPTIVAR™ was more effective than its vehicle in relieving itching associated with allergic conjunctivitis.