Genetic and Pharmacokinetic Determinants of Response to Transdermal Nicotine in White, Black, and Asian Nonsmokers. Issue 6 (9th August 2013)

• Record Type: Journal Article
• Authors: Dempsey, D A; St.Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L
• Is Part Of: Clinical pharmacology & therapeutics. Volume 94:Issue 6(2013)
• Page Start: 687
• Page End: 694
• Publication Date: 2013-08-09
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1038/clpt.2013.159
• Languages: English
• ISSNs: 0009-9236

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never‐smokers. Sixty never‐smokers, balanced for gender and race (white, black, and Asian), wore 7‐mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the <italic>CYP2A6</italic> gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced‐function <italic>CYP2A6</italic> alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.</p> <p> <italic>Clinical Pharmacology &amp; Therapeutics</italic> (2013); <bold>94</bold> 6, 687–694. doi:<ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">10.1038/clpt.2013.159</ext-link></p> </abstract>