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Nicotine & Tobacco Research Advance Access published online on June 12, 2009
Nicotine & Tobacco Research, doi:10.1093/ntr/ntp092
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Urine nicotine metabolite concentrations in relation to plasma cotinine during low-level nicotine exposure

Neal L. Benowitz, Katherine M. Dains, Delia Dempsey, Brenda Herrera, Lisa Yu and Peyton Jacob, III

Neal L. Benowitz, M.D., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center and Department of Biopharmaceutical Sciences, University of California, San Francisco, CA
Katherine M. Dains, Ph.D., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center and Department of Biopharmaceutical Sciences, University of California, San Francisco, CA
Delia Dempsey, M.D., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center and Department of Biopharmaceutical Sciences, University of California, San Francisco, CA
Brenda Herrera, B.S., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center and Department of Biopharmaceutical Sciences, University of California, San Francisco, CA
Lisa Yu, B.S., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center and Department of Biopharmaceutical Sciences, University of California, San Francisco, CA
Peyton Jacob III, Ph.D., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center and Department of Biopharmaceutical Sciences, University of California, San Francisco, CA

Corresponding Author:Neal L. Benowitz, M.D., Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, Medical Service, San Francisco General Hospital Medical Center, University of California, San Francisco, Box 1220, San Francisco, CA 94143-1220, USA. Telephone: 4150-206-8324; Fax: 415-206-4956; E-mail: NBenowitz{at}MedSFGH.ucsf.edu


  Abstract

Introduction: Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined.

Methods: We dosed 36 nonsmokers with 100, 200, or 400 µg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr.

Results: A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 µg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone.

Discussion: Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.

Received: August 12, 2008; Accepted: January 27, 2009
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