Publications by authors named "Rodger D Kempsford"

2 Publications

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The efficacy of once-daily fluticasone furoate/vilanterol in asthma is comparable with morning or evening dosing.

Respir Med 2013 Dec 5;107(12):1873-80. Epub 2013 Nov 5.

Medicines Research Centre, GlaxoSmithKline, Stevenage SG1 2NY, UK. Electronic address:

Aim: To investigate the effect of time of day of dosing (morning or evening) on lung function following administration of fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg.

Methods: Double-blind, placebo-controlled, randomised, three-way crossover study. Subjects with persistent asthma (N = 26) received FF/VI (morning or evening) or matching placebo once-daily for 14 (± 2 days) via dry powder inhaler (DPI). Weighted mean (0-24h) and pre-treatment FEV1 (morning and evening) were determined after the Day 14 evening dose, together with mean pre-treatment (morning and evening) peak expiratory flow (PEF) on Days 2-12.

Results: FF/VI 100/25 administered morning or evening produced clinically significant increases in weighted mean FEV1: the differences [95% confidence interval (CI)] from placebo were 377 mL [293, 462] and 422 mL [337, 507], respectively; the difference between morning and evening dosing was -44 mL [-125, 36]. Day 14 pre-treatment morning FEV1 differences [95% CI] from placebo were 403 mL [272, 533] and 496 mL [369, 624] after morning and evening dosing, respectively; the morning:evening treatment difference was -94 mL [-221, 34]. Pre-treatment evening FEV1 differences [95% CI] from placebo were 275 mL [169, 380] and 309 mL [205, 413] after morning and evening dosing, respectively; the morning:evening treatment difference was -34 mL [-138, 70]. FF/VI (morning or evening) produced rapid increases in PEF with the full effect apparent after the first dose and maintained throughout the 14-day treatment period.

Conclusion: FF/VI 100/25 produces comparable improvements in lung function whether dosed in the morning or evening in subjects with persistent asthma.
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http://dx.doi.org/10.1016/j.rmed.2013.07.002DOI Listing
December 2013

Metabolism and disposition of vilanterol, a long-acting β(2)-adrenoceptor agonist for inhalation use in humans.

Drug Metab Dispos 2013 Jan 4;41(1):89-100. Epub 2012 Oct 4.

Division of Drug Metabolism and Pharmacokinetics, GlaxoSmithKline R&D, Park Road, Ware, Hertfordshire, SG12 0DP, United Kingdom.

The metabolism and disposition of vilanterol, a novel long-acting β(2)-adrenoceptor agonist (LABA) for inhalation use, was investigated after oral administration in humans. Single oral administrations of up to 500 μg of vilanterol were shown to be safe and well tolerated in two clinical studies in healthy men. In a human radiolabel study, six healthy men received a single oral dose of 200 μg of [(14)C]vilanterol (74 kBq). Plasma, urine, and feces were collected up to 168 hours after the dose and were analyzed for vilanterol, metabolites, and radioactivity. At least 50% of the radioactive dose was orally absorbed. The primary route of excretion of drug-related material was via O-dealkylation to metabolites, which were mainly excreted in urine. Vilanterol represented a very small percentage (<0.5%) of the total drug-related material in plasma, indicative of extensive first-pass metabolism. Circulating metabolites resulted mainly from O-dealkylation and exhibited negligible pharmacologic activity. The therapeutic dose level for vilanterol is 25 μg by the inhalation route. At this low-dose level, the likelihood of pharmacologically inactive metabolites causing unexpected toxicity is negligible. In addition to providing an assessment of the disposition of vilanterol in human, this work highlights a number of complexities associated with determining human absorption, distribution, metabolism, and excretion (ADME) for inhaled molecules--mainly related to the low chemical doses and complications associated with the inhalation route of administration.
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http://dx.doi.org/10.1124/dmd.112.048603DOI Listing
January 2013