This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.

This paper synthesizes the main findings from the 2016 FDA-sponsored workshop focused on biomarkers of potential harm (BOPH) and highlights research areas that could further strengthen the science around BOPH and their applicability to tobacco regulatory science.

ObjectiveThis scoping review provides an overview of the existing literature on biomarkers of exposure from electronic nicotine delivery systems (ENDS) use and identifies gaps in existing knowledge.Data sourcesWe searched two international databases (PubMed and Web of Science) to identify relevant studies published from August 2013 to February 2021.Data selectionStudies were included if they assessed and compared biomarkers of exposure between exclusive ENDS users, non-users, exclusive cigarette smokers, dual users of ENDS and cigarettes or cigarette smokers who switch to ENDS.Data extraction and synthesisOf the 5074 studies identified, 188 studies met criteria and were selected for full-text screening. Of these, 27 studies were selected for inclusion and data extraction.ConclusionsConsistent, although limited, evidence shows that exclusive ENDS users have elevated levels of biomarkers of certain volatile organic compounds (VOCs; eg, acrylamide and acrylonitrile), metals (eg, cadmium and selenium) and propylene glycol compared with non-users; however, evidence for biomarkers of other toxicants (eg, acrolein, benzene and chromium) is mixed. Biomarkers of most VOCs are lower in ENDS users compared with cigarette smokers, and cigarette smokers who switch to ENDS consistently show reductions in VOC biomarkers. Evidence comparing metal exposures from exclusive ENDS use, cigarette smoking and dual use is mixed and depends on the metal. ENDS and e-liquid characteristics as well as use patterns may be associated with elevated exposure to VOCs and metals. Additional rigorous, controlled studies can assess biomarker exposures from ENDS use and inform the overall risk–benefit of ENDS use for different user populations.

Introduction The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative cohort of tobacco product users and nonusers. The study’s main purpose is to obtain longitudinal epidemiologic data on tobacco use and exposure among the US population. Aims and Methods Nicotine biomarkers—cotinine (COT) and trans-3′-hydroxycotinine (HCT)—were measured in blood samples collected from adult daily tobacco users and nonusers during Wave 1 of the PATH Study (2013–2014; n = 5012; one sample per participant). Participants’ tobacco product use and exposure to secondhand smoke were categorized based on questionnaire responses. Nonusers were subdivided into never users and recent former users. Daily tobacco users were classified into seven tobacco product use categories: exclusive users of cigarette, smokeless tobacco, electronic cigarette, cigar, pipe, and hookah, as well as polyusers. We calculated sample-weighted geometric mean (GM) concentrations of cotinine, HCT, and the nicotine metabolite ratio (NMR) and evaluated their associations with tobacco use with adjustment for potential confounders. Results The GMs (95% confidence intervals) of COT and HCT concentrations for daily tobacco users were 196 (184 to 208) and 72.5 (67.8 to 77.4) ng/mL, and for nonusers they were 0.033 (0.028 to 0.037) and 0.021 (0.018 to 0.023) ng/mL. Exclusive smokeless tobacco users had the highest COT concentrations of all user groups examined. The GM NMR in daily users was 0.339 (95% confidence interval: 0.330 to 0.350). Conclusions These nationally representative estimates of serum nicotine biomarkers could be the basis for reference ranges characterizing nicotine exposure for daily tobacco users and nonusers in the US adult population. Implications This report summarizes the serum nicotine biomarker measurements in Wave 1 of the PATH Study. We are reporting the first estimates of HCT in serum for daily tobacco users and nonusers in the noninstitutionalized, civilian US adult population; the first nationally representative serum COT estimates for daily exclusive users of different tobacco products and daily polyusers; and the first nationally representative estimate of the serum NMR in daily tobacco users by age, race/ethnicity, and sex.