Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1.   Pharmacodynamic Properties
Anti-allergic
ATC code: SO1GX07

Azelastine, a phthalazinone derivative is classified as a potent long-acting anti-allergic compound with selective H1 antagonist properties. An additional anti-inflammatory effect could be detected after topical ocular administration.

Data from in vivo (pre-clinical) and in vitro studies show that azelastine inhibits the synthesis or release of the chemical mediators known to be involved in early and late stage allergic reactions e.g. leukotriene, histamine, PAF and serotonin.

To date, long term therapy ECG evaluations of patients treated with high oral doses of azelastine, have shown that in multiple dose studies, there is no clinically significant effect of azelastine on the corrected QT (QTc) interval.

No association of azelastine with ventricular arrhythmia or torsade de pointes was observed in over 3700 patients treated with oral azelastine.

Relief of symptoms of allergic conjunctivitis should be noticed after 15-30 minutes.

Pharmacokinetic Properties

5.2.   Pharmacokinetic Properties

General characteristics (systemic pharmacokinetics)
Following oral administration azelastine is rapidly absorbed showing an absolute bioavailability of 81%. Food has no influence on absorption. The volume of distribution is high indicating distribution predominantly into the periphery. The level of protein binding is relatively low (80-90%, a level too low to give concern over drug displacement reactions).

Plasma elimination half- lives after a single dose of azelastine are approximately 20 hours for azelastine and about 45 hours for the therapeutically active main metabolite N-Desmethyl azelastine. Excretion occurs mainly via the faeces. The sustained excretion of small amounts of the dose in the faeces suggests that some enterohepatic circulation may take place.

Characteristics in patients (ocular pharmacokinetics)

After repeated ocular application of Optilast eye drops (up to one drop in each eye, four times daily), Cmax steady state plasma levels of azelastine hydrochloride were very low and were detected at or below the limit of quantification.