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Liakoni E, Tyndale RF, Jacob P, et al. Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance. Pharmacogenet Genomics. 2021;31(5):97-107doi: 10.1097/FPC.0000000000000427.
Liakoni, E., Tyndale, R. F., Jacob, P., Dempsey, D. A., Addo, N., & Benowitz, N. L. (2021). Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance. Pharmacogenetics and genomics, 31(5), 97-107. https://doi.org/10.1097/FPC.0000000000000427
Liakoni, Evangelia, et al. "Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance." Pharmacogenetics and genomics vol. 31,5 (2021): 97-107. doi: https://doi.org/10.1097/FPC.0000000000000427
Liakoni E, Tyndale RF, Jacob P, Dempsey DA, Addo N, Benowitz NL. Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance. Pharmacogenet Genomics. 2021 Jul 01;31(5):97-107. doi: 10.1097/FPC.0000000000000427. PMID: 33675323; PMCID: PMC8184575.
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Pharmacogenet Genomics. 2021 Jul 01;31(5):97-107. doi: 10.1097/FPC.0000000000000427.

Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance.

Pharmacogenetics and genomics

Evangelia Liakoni, Rachel F Tyndale, Peyton Jacob, Delia A Dempsey, Newton Addo, Neal L Benowitz

Affiliations

  1. Department of Medicine, Program in Clinical Pharmacology, Division of Cardiology, University of California, San Francisco, California, USA.
  2. Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
  3. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto.
  4. Department of Pharmacology & Toxicology.
  5. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
  6. Center for Tobacco Control Research and Education, University of California, San Francisco, California, USA.

PMID: 33675323 PMCID: PMC8184575 DOI: 10.1097/FPC.0000000000000427

Abstract

OBJECTIVES: To investigate if the nicotine metabolite ratio (NMR, the ratio of nicotine metabolites 3'-hydroxycotinine/cotinine) is a reliable phenotypic biomarker for nicotine clearance across races, and as a function of differences in the rate of nicotine, cotinine and 3'-hydroxycotinine glucuronidation and UGT genotypes.

METHODS: Participants [Caucasians (Whites), African Americans (Blacks) and Asian-Americans (Asians)] received an oral solution of deuterium-labeled nicotine and its metabolite cotinine. Plasma and saliva concentrations of nicotine and cotinine were used to determine oral clearances. Rates of glucuronidation were assessed from urine glucuronide/parent ratios, and UGT2B10 and UGT2B17 genotypes from DNA.

RESULTS: Among the 227 participants, 96 (42%) were White, 67 (30%) Asian and 64 (28%) Black. Compared to the other two races, Whites had higher nicotine and cotinine total oral clearance, Blacks had lower nicotine and cotinine glucuronidation rates and Asians had lower 3'-hydroxycotinine glucuronidation rates. A strong positive correlation (correlations coefficients 0.77-0.84; P < 0.001) between NMR and nicotine oral clearance was found for all three races, and NMR remained a strong predictor for the nicotine oral clearance while adjusting for race, sex and age. Neither the metabolite glucuronidation ratios nor the UGT genotypes had significant effects on the ability of NMR to predict nicotine oral clearance.

CONCLUSION: NMR appears to be a reliable phenotypic biomarker for nicotine clearance across races, glucuronidation phenotypes and genotypes. Racial differences in the relationships between NMR, smoking behaviors and addiction are unlikely to be related to an inadequate estimation of nicotine clearance on the basis of NMR.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

References

  1. Pediatrics. 2008 Sep;122(3):e643-7 - PubMed
  2. Clin Pharmacol Ther. 2006 May;79(5):480-8 - PubMed
  3. Pharmacol Biochem Behav. 2016 Sep;148:1-7 - PubMed
  4. Clin Pharmacol Ther. 2004 Jul;76(1):64-72 - PubMed
  5. J Pers Med. 2017 Dec 01;7(4): - PubMed
  6. Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1396-400 - PubMed
  7. Cancer Epidemiol Biomarkers Prev. 2017 Jul;26(7):1093-1099 - PubMed
  8. Pharmacogenet Genomics. 2014 Mar;24(3):172-6 - PubMed
  9. Clin Pharmacol Ther. 2009 Jun;85(6):635-43 - PubMed
  10. Clin Pharmacol Ther. 1993 Mar;53(3):316-23 - PubMed
  11. Handb Exp Pharmacol. 2009;(192):29-60 - PubMed
  12. Am J Hum Genet. 2008 Sep;83(3):337-46 - PubMed
  13. Clin Pharmacol Ther. 1994 Nov;56(5):483-93 - PubMed
  14. J Pharmacol Exp Ther. 2010 Jan;332(1):202-9 - PubMed
  15. J Anal Toxicol. 2006 Jul-Aug;30(6):386-9 - PubMed
  16. Pharmacogenet Genomics. 2016 Jul;26(7):340-50 - PubMed
  17. Pharmacol Biochem Behav. 2009 Mar;92(1):6-11 - PubMed
  18. Cancer Res. 2010 Oct 1;70(19):7543-52 - PubMed
  19. Annu Rev Pharmacol Toxicol. 2009;49:57-71 - PubMed
  20. Mol Pharmacol. 2007 Sep;72(3):761-8 - PubMed
  21. J Pharm Biomed Anal. 2000 Sep;23(4):653-61 - PubMed
  22. Mol Psychiatry. 2020 Mar 10;: - PubMed
  23. Addict Biol. 2020 Jan;25(1):e12741 - PubMed
  24. Drug Metab Dispos. 2007 Oct;35(10):1935-41 - PubMed
  25. Carcinogenesis. 2014 Nov;35(11):2526-33 - PubMed
  26. Pharmacogenet Genomics. 2017 Apr;27(4):143-154 - PubMed
  27. Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):94-104 - PubMed
  28. Cancer Epidemiol Biomarkers Prev. 2020 Apr;29(4):871-879 - PubMed
  29. J Pharmacol Exp Ther. 1999 Dec;291(3):1196-203 - PubMed
  30. Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1105-14 - PubMed
  31. Lancet Respir Med. 2015 Feb;3(2):131-138 - PubMed
  32. Clin Pharmacol Ther. 2008 Sep;84(3):320-5 - PubMed
  33. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 1;879(3-4):267-76 - PubMed
  34. Clin Pharmacol Ther. 2006 Jun;79(6):600-8 - PubMed
  35. PLoS One. 2013 Aug 02;8(8):e70938 - PubMed
  36. Pharmacol Rev. 2005 Mar;57(1):79-115 - PubMed
  37. Drug Alcohol Depend. 2000 Jul 1;60(1):13-8 - PubMed

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