Emadine Pharmacology, Pharmacokinetics, Studies, Metabolism - Emedastine

Emadine Pharmacology, Pharmacokinetics, Studies, Metabolism - Emedastine

CLINICAL PHARMACOLOGY

Emedastine is a relatively selective, histamine H ₁ antagonist. In vitro examinations of emedastine's affinity for histamine receptors (H ₁ : Ki=1.3 nM, H ₂ : Ki=49,067 nM, and H ₃ : Ki=12,430 nM) demonstrate relative selectivity for the H ₁ histamine receptor. In vivo studies have shown concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration. Emedastine appears to be devoid of effects on adrenergic, dopaminergic and serotonin receptors.

Following topical administration in man, emedastine was shown to have low systemic exposure. In a study involving 10 normal volunteers dosed bilaterally twice daily for 15 days with emedastine ophthalmic solution 0.05%, 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 elimination half-life of oral emedastine in plasma is 3-4 hours. Approximately 44% of the oral dose is recovered in the urine over 24 hours with only 3.6% of the dose excreted as parent drug. Two primary metabolites, 5- and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms. The 5'-oxoanalogs of 5- and 6-hydroxy-emedastine and the N-oxide are also formed as minor metabolites.

In an environmental study, patients with allergic conjunctivitis were treated with EMADINE for six weeks. The results demonstrated that EMADINE provides relief of the signs and symptoms of allergic conjunctivitis.

In conjunctival antigen challenge studies, in which subjects were challenged with antigen both initially and up to four hours after dosing, EMADINE was demonstrated to be significantly more effective than placebo in preventing ocular itching associated with allergic conjunctivitis.