Open AccessA Novel Method for Studying the Pharmacokinetics of [ 14 C]Umeclidinium After Application to the Axilla or Palm of Healthy Male Subjects
Author(s) -
Pene Dumitrescu T,
Santos LL,
Hughes SC,
Pereira AI,
Young GC,
Hussey E,
Charlton P,
BaptisteBrown S,
Stuart JS,
Vincent V,
Marle SP,
Schmith VD
Publication year - 2016
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12406
Subject(s) - pharmacokinetics , axilla , medicine , dosing , pharmacology , anticholinergic , anesthesia , tolerability , population , adverse effect , cancer , breast cancer , environmental health
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 [ 14 C]UMEC applied to either unoccluded axilla (UA), occluded axilla (OA), or occluded palm (OP) of healthy males. After 8 h the formulation was removed. [ 14 C]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.