A Novel Method for Studying the Pharmacokinetics of [14C]Umeclidinium After Application to the Axilla or Palm of Healthy Male Subjects

Umeclidinium (UMEC), a long‐acting muscarinic antagonist approved for chronic obstructive pulmonary disease (COPD), was investigated for primary hyperhidrosis as topical therapy. This study evaluated the pharmacokinetics, safety, and tolerability of a single dose of [14C]UMEC applied to either unocc...

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Bibliographic Details
Published in:Clinical and translational science 2016-08, Vol.9 (4), p.183-191
Main Authors: Pene Dumitrescu, T, Santos, LL, Hughes, SC, Pereira, AI, Young, GC, Hussey, E, Charlton, P, Baptiste‐Brown, S, Stuart, JS, Vincent, V, Marle, SP, Schmith, VD
Format: Article
Language:English
Subjects:
Absorption
Acetylcholine receptors (muscarinic)
Administration, Inhalation
Adult
Axilla - physiology
Bioavailability
Carbon Radioisotopes - pharmacokinetics
Chronic obstructive pulmonary disease
Computer simulation
Conflicts of interest
Demography
Dose-Response Relationship, Drug
Drug Administration Routes
Drug dosages
Exposure
Hand - physiology
Humans
Intravenous administration
Lung diseases
Male
Males
Mass spectrometry
Mass spectroscopy
Middle Aged
Models, Biological
Obstructive lung disease
Occlusion
Pharmacokinetics
Population
Quinuclidines - administration & dosage
Quinuclidines - adverse effects
Quinuclidines - blood
Quinuclidines - pharmacokinetics
Radioactivity
Regulatory approval
Skin
Stock options
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Summary:Umeclidinium (UMEC), a long‐acting muscarinic antagonist approved for chronic obstructive pulmonary disease (COPD), was investigated for primary hyperhidrosis as topical therapy. This study evaluated the pharmacokinetics, safety, and tolerability of a single dose of [14C]UMEC applied to either unoccluded axilla (UA), occluded axilla (OA), or occluded palm (OP) of healthy males. After 8 h the formulation was removed. [14C]UMEC plasma concentrations (Cp) were quantified by accelerator mass spectrometry. Occlusion increased systemic exposure by 3.8‐fold. Due to UMEC absorption‐limited pharmacokinetics, Cp data from the OA were combined with intravenous data from a phase I study. The data were described by a two‐compartment population model with sequential zero and first‐order absorption and linear elimination. Simulated systemic exposure following q.d. doses to axilla was similar to the exposure from the inhaled therapy, suggesting that systemic safety following dermal administration can be bridged to the inhaled program, and offering the potential for a reduced number of studies and/or subjects.
ISSN:1752-8054
1752-8062
DOI:10.1111/cts.12406