Vilanterol

Danger

H302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]

P260, P264, P270, P273, P301+P317, P308+P316, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Vilanterol is a selective long-acting beta2-adrenergic agonist. Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs.

The effective half-life for vilanterol, as determined from inhalation administration of multiple doses, is 11 hours. The plasma elimination half-life, as determined from inhalation administration of multiple doses of vilanterol 25 mcg, is 21.3 hours in patients with COPD and 16.0 hours in patients with asthma. For a single dose inhaled administration, the plasma elimination phase half-life averaged 2.5 hour.

Vilanterol is principally metabolized by cytochrome p450 3A4 (CYP3A4) to a range of metabolites with significantly reduced beta1- and beta2-agonist activity. The major route of metabolism was via O-dealkylation, with up to 78% of the recovered dose eliminated as O-dealkylated metabolites while N-Dealkylation and C-dealkylation were minor pathways, representing 5% of the recovered dose.

028LZY775B

VILANTEROL

Mechanisms of Action [MoA] - Adrenergic beta2-Agonists

Established Pharmacologic Class [EPC] - beta2-Adrenergic Agonist

Vilanterol is a beta2-Adrenergic Agonist. The mechanism of action of vilanterol is as an Adrenergic beta2-Agonist.

Vilanterol plasma levels may not predict therapeutic effects. Following inhaled administration of vilanterol in healthy subjects, Cmax occurred at 5 to 15 minutes. Vilanterol is mostly absorbed from the lung after inhaled doses with negligible contribution from oral absorption. Following repeat dosing of inhaled vilanterol, the steady state was achieved within 14 days with up to 1.7-fold accumulation. The absolute bioavailability of vilanterol when administered by inhalation was 27.3%, primarily due to absorption of the inhaled portion of the dose delivered to the lung. Oral bioavailability from the swallowed portion of the dose of vilanterol is low (<2%) due to extensive first-pass metabolism. Systemic exposure (AUC) in patients with COPD was 24% higher than observed in healthy subjects. Systemic exposure (AUC) in patients with asthma was 21% lower than observed in healthy subjects.