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Pulmonary elimination rate of inhaled 99m Tc‐sestamibi radioaerosol is delayed in healthy cigarette smokers
Author(s) -
Ruparelia Prina,
Cheow Heok K.,
Evans John W.,
Banney Leith,
Shankar Sonal,
Szczepura Katherine R.,
Swift Anna E.,
Ballinger James R.,
Hartman Neil G.,
Chilvers Edwin R.,
Peters A. Michael
Publication year - 2008
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2008.03099.x
Subject(s) - medicine , inhalation , lung , in vivo , p glycoprotein , biomarker , ex vivo , respiratory disease , technetium , pathology , gastroenterology , nuclear medicine , anesthesia , drug resistance , chemistry , microbiology and biotechnology , biochemistry , multiple drug resistance , biology
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Very little is known about the physiology of P‐glycoprotein (P‐gp) expression in the lungs. • Ex vivo evidence based on resected lung tissue suggests that pulmonary P‐gp is upregulated by cigarette smoke, but there are no in vivo studies to date. WHAT THIS STUDY ADDS • The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled 99m Tc‐sestamibi, a P‐gp substrate, provides for the first time a potential method for quantifying functional pulmonary P‐gp expression that may inform about drug therapy by inhalation as well as provide a non‐invasive, quantitative, human biomarker for assessing P‐gp modulators. AIM To explore inhaled technetium‐99m‐labelled hexakis‐methoxy‐isobutyl isonitrile ( 99m Tc‐sestamibi) for quantifying pulmonary P‐glycoprotein (P‐gp) expression. METHODS The elimination rate from the lungs of 99m Tc‐sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease. RESULTS 99m Tc‐sestamibi elimination rates [% min −1 (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated. CONCLUSION Cigarette smoke upregulates lung P‐gp. 99m Tc‐sestamibi elimination in normal smokers could be used to test new P‐gp modulators. The findings also have implications for inhaled drug delivery.