Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: decongestants and antiallergics; other antiallergics, 
ATC code: SO1G X 06

Emedastine is a potent selective and topically effective histamine H 1 antagonist (K, = 1.3 nM).
In vitro examinations of emedastine's affinity for histamine receptors (H1,H2 ,H3) demonstrate 10,000-fold selectivity for the H 1 receptor, K's = 1.3 nM, 49,064 nM and 12, 430 nM,respectively.In vivo topica! ocular administration of emedastine produces a concentration- dependent inhibition of histamine-stimulated conjunctival vascular permeability. Studies with emedastine have not shown effects on adrenergic, dopaminergic, and serotonin receptors.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
Emedastine is absorbed systemically, as are other topically administered drug substances. In a study involving ten normal volunteers dosed bilaterally twice daily for 15 days with EMADINE 0.5 mg/ml eye drops solution, plasma concentrations of the parent compound were generally below the quantitation limit of the assay (0.3 ng/ml). Samples in which emedastine was quantifiable ranged from 0.30 to 0.49 ng/ml.

The human oral bioavailability of emedastine is approximately 50% and maximum plasma Concentrations were achieved within one-two hours after dosing.

Metabolism
Emedastine is principally metabolised by the liver. The elimination half-life of topical emedastine is ten hours. Approximately 44% of an oral dose is recovered in the urine over 24 hours, with only 3.6% of the dose excreted as parent drug substance. two primary metabolites, 5-and 6- hydroxyemedastine, are excreted in the urine as both free and conjugated forms. The 5'-oxo analogues of 5-and 6-hydroxyemedastine and the N-oxide are also formed as minor metabolites.