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INTRODUCTION There is overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema, and other serious diseases in smokers. In the Total Exposure Study, 29 biomarkers of potential harm (BOPH) were measured in a cross-sectional sample of 3,585 adult smokers (AS) and 1,077 nonsmokers (NS). The BOPH included(More)
INTRODUCTION There are about 4,800 different chemical constituents in cigarette smoke. Therefore, the total systemic exposure evaluation of the population of smokers to cigarette smoke is challenging. Measurement of biomarkers as surrogates of cigarette smoke constituents is a realistic approach to assess exposure. OBJECTIVE To estimate cigarette smoke(More)
AIMS To develop a population-based model to describe and predict the pharmacokinetics of carboxyhaemoglobin (COHb) in adult smokers. METHODS Data from smokers of different conventional cigarettes (CC) in three open-label, randomized studies were analysed using NONMEM (version V, Level 1.1). COHb concentrations were determined at baseline for two(More)
Cigarette smoke is a complex aerosol that includes a gas vapor phase and a particulate phase. Inclusion of activated carbon in the cigarette filter can reduce some of the gas-phase smoke constituents implicated as toxicologically relevant. The present study evaluated exposure to selected gas-phase constituents when adult smokers switched to prototype(More)
INTRODUCTION It has been reported that adult smokers (AS) may be considering smokeless tobacco products as an alternative to smoking. The objective of this study was to evaluate the change in exposure in AS using Marlboro snus (MSNUS) (a tobacco pouch product in test market in June 2007). METHODS AS were randomized into the following groups--CS: subjects(More)
Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of(More)
Some quinolone antibiotics cause increases in levels of theophylline in plasma that lead to serious adverse effects. We investigated the mechanism of this interaction by developing an in vitro system of human liver microsomes. Theophylline (1,3-dimethylxanthine) was incubated with human liver microsomes in the presence of enoxacin, ciprofloxacin,(More)
One of the carcinogens from cigarette smoke, 4-aminobiphenyl, is excreted in urine as 4-N-hydroxyl aminobiphenyl metabolite conjugates that undergo pH mediated activation to nitreneum ions leading to bladder tumorigenesis via DNA adduct formation. We hypothesize that changing the pH of smokers' urine might impact the mutagenic outcome. 4-NOHABP was(More)
Nasal delivery is a potential alternative for systemic availability of drugs restricted to intravenous administration, such as peptide and protein drugs. Although nasal delivery avoids the hepatic first-pass effect, the enzymatic barrier of the nasal mucosa creates a pseudo-first-pass effect. The xenobiotic metabolic activity in the nasal epithelium has(More)
Theophylline is metabolized in the liver by one or more cytochrome P-450 enzymes. To assess the amounts and types of these human cytochromes P-450, we incubated theophylline with microsomes prepared from 22 different human livers in the presence of NADPH, and measured simultaneous rates of 1- and 3-N-demethylations to 3-methylxanthine (3-MX) and(More)