Vilanterol, a novel inhaled long-acting β2 adrenoceptor agonist (LABA), demonstrates extensive first pass clearance to metabolites with negligible pharmacological activity in man

Introduction: Vilanterol (VI) trifenatate is a novel LABA with demonstrated 24-hour clinical duration of action, currently in development in combination with an inhaled corticosteroid for once-daily treatment of COPD & asthma. Objectives: The excretion and metabolism of radio-labelled VI was investigated following oral dosing to represent the swallowed portion of an inhaled dose. Methods: Open label, single dose study. Healthy male subjects [N=6] received an oral solution dose of 200 ug of [ 14 C]VI (2 uCi). Plasma samples and all urine and faeces were collected up to 168 h post dose and analysed for total radioactivity, VI and VI metabolites (as appropriate). Results: VI was well absorbed (>50% of the radioactive dose). VI represented a very small percentage ( Conclusion: VI undergoes extensive first-pass metabolism in man. VI was well tolerated after an oral dose (200 ug) considerably in excess of the likely clinical inhaled dose (25 ug), indicating absent pharmacological activity of the metabolites in man (in agreement with pre-clinical data). Funded by GSK (B2C106181; NCT01286831)