Metabolism and Disposition of Vilanterol, a Long-Acting β2-Adrenoceptor Agonist for Inhalation Use in Humans

• DOI: 10.1124/dmd.112.048603
• Publication Date: 2012-10-06T02:22:23Z
• Authors: Andrew W Harrell; Sarah K Siederer; Jo Bal; Nainesh H Patel; Graeme C Young; Clive C Felgate; Sebastian J Pearce; Andy D Roberts; Claire Beaumont; Amanda J Emmons; Adrian I Pereira; Rodger D Kempsford
• Keywords: ADME

The metabolism and disposition of vilanterol, a novel long-acting <i>β</i>₂-adrenoceptor agonist (LABA) for inhalation use, was investigated after oral administration in humans. Single administrations up to 500 <i>μ</i>g vilanterol were shown be safe well tolerated two clinical studies healthy men. In human radiolabel study, six men received single dose 200 [¹⁴C]vilanterol (74 kBq). Plasma, urine, feces collected 168 hours the analyzed metabolites, radioactivity. At least 50% radioactive orally absorbed. primary route excretion drug-related material via <i>O</i>-dealkylation which mainly excreted urine. Vilanterol represented very small percentage (&lt;0.5%) total plasma, indicative extensive first-pass metabolism. Circulating metabolites resulted from exhibited negligible pharmacologic activity. therapeutic level is 25 by route. this low-dose level, likelihood pharmacologically inactive causing unexpected toxicity negligible. addition providing an assessment human, work highlights number complexities associated with determining absorption, distribution, metabolism, (ADME) inhaled molecules—mainly related low chemical doses complications administration.