Generally, 70-80% of absorbed nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. There is genetic polymorphism in the human CYP2A6 gene. Among several mutated alleles, CYP2A6*4 allele is a whole deleted type. The purpose of the present study was to clarify the metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for nicotine and its nine metabolites. Excretion levels of nicotine and its metabolites in 24 h accumulated urine after the chewing of one piece of nicotine gum were evaluated in five Japanese subjects whose CYP2A6 genotype was determined. In three subjects with CYP2A6*1A/CYP2A6*1A, CYP2A6*1A/CYP2A6*1B, and CYP2A6*1A/CYP2A6*4 (group I), nicotine was mainly excreted as cotinine, trans-3'-hydroxycotinine, and their glucuronide (approximately 60%). In contrast, in two subjects with CYP2A6*4/CYP2A6*4 (group II), trace levels of cotinine, cotinine N-glucuronide, and cotinine 1'-N-oxide were detected. Trans-3'-hydroxycotinine and its O-glucuronide were not detected. The excretion levels of nicotine itself, nicotine N-glucuronide, and nicotine 1'-N-oxide were higher than those in the other three subjects. The total excretion levels of these three compounds were approximately 95% in group II versus 35% in group I. However, the sum of the excretion levels of nicotine and all metabolites was similar among these five subjects. This is the first report of the metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejps.2004.04.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrating genetic and clinical data to predict lung cancer in patients with chronic obstructive pulmonary disease.
BMC Pulm Med
December 2024
Department of Integrative Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Background: Chronic obstructive pulmonary disease (COPD) is closely linked to lung cancer (LC) development. The aim of this study is to identify the genetic and clinical risk factors for LC risk in COPD, according to which the prediction model for LC in COPD was constructed.
Methods: This is a case-control study in which patientis with COPD + LC as the case group, patientis with only COPD as the control group, and patientis with only LC as the second control group.
Elucidating the Metabolism of Chiral PCB95 in Wildtype and Transgenic Mouse Models with Altered Cytochrome P450 Enzymes Using Intestinal Content Screening.
Chem Res Toxicol
December 2024
Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242, United States.
Polychlorinated biphenyls (PCBs), such as 2,2',3,5',6-pentachlorobiphenyl (PCB95), are persistent organic pollutants associated with adverse health outcomes, including developmental neurotoxicity. PCB95 is a chiral neurotoxic PCB congener atropselectively metabolized to potentially neurotoxic metabolites in vivo. However, the metabolic pathways of most PCB congeners, including PCB95, remain unknown.
View Article and Find Full Text PDFCirculating metabolites of Borneolum syntheticum (Bingpian) ameliorate atherosclerosis in ApoE mice via inhibiting macrophage foam-cell formation.
Acta Pharmacol Sin
October 2024
Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited.
View Article and Find Full Text PDFIdentification of non-adherence to adjuvant letrozole using a population pharmacokinetics approach in hormone receptor-positive breast cancer patients.
Eur J Pharm Sci
August 2024
Cancer Research Center of Toulouse (CRCT), Inserm U1037, Université Paul Sabatier - Toulouse III, 2 Avenue Hubert Curien, Toulouse 31100, France. Electronic address:
Background: Letrozole, an aromatase inhibitor metabolised via CYP2A6 and CYP3A4/5 enzymes, is used as adjuvant therapy for women with hormone receptor (HR)-positive early breast cancer. The objective of this study was to quantify the impact of CYP2A6 genotype on letrozole pharmacokinetics (PK), to identify non-adherent patients using a population approach and explore the possibility of a relationship between non-adherence and early relapse.
Methods: Breast cancer patients enrolled in the prospective PHACS study (ClinicalTrials.
Pharmacokinetics and Pharmacodynamics of Inhaled Nicotine Salt and Free-Base Using an E-cigarette: A Randomized Crossover Study.
Nicotine Tob Res
September 2024
Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Introduction: Popular "pod-style" e-cigarettes commonly use nicotine salt-based e-liquids that cause less irritation when inhaled and can deliver higher nicotine concentrations than free-base nicotine. This study investigated the pharmacokinetic and pharmacodynamic effects of different nicotine formulations (salt vs. free-base) and concentrations that might influence systemic nicotine absorption and appeal of e-cigarettes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!