Evangelia Liakoni1, Gideon St Helen2, Delia A Dempsey3, Peyton Jacob4, Rachel F Tyndale5, Neal L Benowitz6. 1. Clinical Pharmacology Research Program, Division of Cardiology, Zuckerberg San Francisco General, Department of Medicine, University of California, San Francisco, CA 94143-1220, USA; Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland. 2. Clinical Pharmacology Research Program, Division of Cardiology, Zuckerberg San Francisco General, Department of Medicine, University of California, San Francisco, CA 94143-1220, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA 94143-1390, USA. Electronic address: Gideon.StHelen@ucsf.edu. 3. Clinical Pharmacology Research Program, Division of Cardiology, Zuckerberg San Francisco General, Department of Medicine, University of California, San Francisco, CA 94143-1220, USA. 4. Clinical Pharmacology Research Program, Division of Cardiology, Zuckerberg San Francisco General, Department of Medicine, University of California, San Francisco, CA 94143-1220, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA 94143-1390, USA; Department of Psychiatry, University of California, San Francisco, CA 94143-0482, USA. 5. Pharmacology, Toxicology and Psychiatry, University of Toronto, 4326-1 Kings College Circle, M5S 1A8, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 6. Clinical Pharmacology Research Program, Division of Cardiology, Zuckerberg San Francisco General, Department of Medicine, University of California, San Francisco, CA 94143-1220, USA; Center for Tobacco Control Research and Education, University of California, San Francisco, CA 94143-1390, USA.
Abstract
BACKGROUND: Blacks bear a disproportionate burden of smoking-related diseases and experience greater difficulty quitting smoking than Whites. Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence. The aim of this study was to evaluate the hypothesis that melanin affects nicotine disposition kinetics in humans. METHODS: Forty-four Black participants were administered intravenous infusions of deuterium-labeled nicotine and cotinine. Plasma concentrations of nicotine and cotinine were measured, and pharmacokinetic parameters were estimated. The constitutive and facultative melanin indexes were measured using a dermaspectrophotometer. RESULTS: The median constitutive melanin index was 60.7 (32.8-134.7) and the median facultative melanin index 68.1 (38.6-127.1). The mean (±SD) nicotine elimination half-life was 136 min (±33.5), clearance was 1237 mL/min (±331), and Vss was 204 L (±66), or 2.6 L/kg (±0.7). No evidence of significant differences was found in nicotine pharmacokinetic parameters by comparing participants in different melanin index quartiles (outliers with very high melanin index had similar pharmacokinetic values to others). Differences were not statistically significant when adjusted for age, BMI, sex and CYP2A6 genotype or the nicotine metabolite ratio (NMR), and no evidence of significant correlations were found between melanin (facultative or constitutive) and the pharmacokinetic parameters of nicotine or cotinine or tobacco dependence measures. CONCLUSIONS: Based on our finding in this group of Black smokers, we could not confirm the hypothesis that melanin significantly affects nicotine disposition kinetics or measures of tobacco dependence.
BACKGROUND: Blacks bear a disproportionate burden of smoking-related diseases and experience greater difficulty quitting smoking than Whites. Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence. The aim of this study was to evaluate the hypothesis that melanin affects nicotine disposition kinetics in humans. METHODS: Forty-four Black participants were administered intravenous infusions of deuterium-labeled nicotine and cotinine. Plasma concentrations of nicotine and cotinine were measured, and pharmacokinetic parameters were estimated. The constitutive and facultative melanin indexes were measured using a dermaspectrophotometer. RESULTS: The median constitutive melanin index was 60.7 (32.8-134.7) and the median facultative melanin index 68.1 (38.6-127.1). The mean (±SD) nicotine elimination half-life was 136 min (±33.5), clearance was 1237 mL/min (±331), and Vss was 204 L (±66), or 2.6 L/kg (±0.7). No evidence of significant differences was found in nicotine pharmacokinetic parameters by comparing participants in different melanin index quartiles (outliers with very high melanin index had similar pharmacokinetic values to others). Differences were not statistically significant when adjusted for age, BMI, sex and CYP2A6 genotype or the nicotine metabolite ratio (NMR), and no evidence of significant correlations were found between melanin (facultative or constitutive) and the pharmacokinetic parameters of nicotine or cotinine or tobacco dependence measures. CONCLUSIONS: Based on our finding in this group of Black smokers, we could not confirm the hypothesis that melanin significantly affects nicotine disposition kinetics or measures of tobacco dependence.
Authors: Simona Pichini; Oscar Garcia-Algar; Laura Muñoz; Oriol Vall; Roberta Pacifici; Cecilia Figueroa; José Antonio Pascual; David Diaz; Jordi Sunyer Journal: J Expo Anal Environ Epidemiol Date: 2003-03
Authors: Hanaa A Galeb; Emma L Wilkinson; Alison F Stowell; Hungyen Lin; Samuel T Murphy; Pierre L Martin-Hirsch; Richard L Mort; Adam M Taylor; John G Hardy Journal: Glob Chall Date: 2020-11-25