Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials.
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ABSTRACT: Methods
Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases.Results
Among 298 articles identified, there were 35 reviewed publications reporting on 33 studies of non-smokers receiving transdermal nicotine for >48hours. In the 16 randomized trials, 7 crossover, 1 case/control and 9 open studies patients received an initial nicotine dose of between 2.5mg and 15mg/day. In 22 studies, daily doses increased by 2 to 7 steps in 3 to 96 days until the dose was between 5mg and 105mg/day. The target nicotine dose was 19.06±20.89mg/day. The 987 non-smokers (534 never-smokers, 326 ex-smokers and 127 classified as "non-smokers") received or did not receive nicotine. The most common side-effects were nausea and skin itching. Forty-three (7.1%) non-smokers stopped treatment because of an adverse event of nicotine. No hospitalization related to nicotine side-effects were reported.Conclusion
Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.
SUBMITTER: Dautzenberg B
PROVIDER: S-EPMC8183099 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7834682 | biostudies-literature
Project description:BackgroundIn 4 decades, numerous nicotine replacement therapy products have been developed. Population pharmacokinetic models can support exposure-response modeling and inform nicotine replacement therapy product development, but only limited model-based cross-study population pharmacokinetic analyses for nicotine replacement therapy products have been published.ObjectivesThe aim of this retrospective analysis was to assess the population pharmacokinetics of nicotine across intravenous, oral, transdermal and oromucosal (mouth spray, chewing gum, lozenge and inhaler) routes and formulations in healthy smoking subjects.MethodsData on 930 unique subjects (46,016 observations) from 29 single- and repeated-dose studies with multiple formulations across intravenous, oral, transdermal and oromucosal routes of administration were included. Data from intravenous and extravascular routes of administration were modelled separately for run efficiency reasons. For developing extravascular models, clearance and disposition parameters and their inter-individual variabilities were fixed to the estimates for intravenously delivered nicotine. Detectable pre-dose nicotine concentrations were modelled as a hypothetical nicotine bolus into the central compartment at the start of wash-out. Modelling repeated-dose oral and buccal administrations required a time-dependent increase in clearance or decrease in bioavailability to describe the data adequately.ResultsDisposition of intravenous nicotine was best described by a three-compartment model with initial and terminal half-lives of 7 min and 4.5 h, respectively, and the absorption of single oral doses was best described with a first-order absorption rate constant of 1.55 h-1. The data of buccal formulations were modelled with parallel oromucosal absorption and gastrointestinal absorption of a part of the dose that is swallowed. For transdermal nicotine, parallel zero- and first-order release from the patch and a transit-compartment absorption model best described the data. Key pharmacokinetic parameters were reliably estimated, with typical values for clearance (67 L/h for a 70-kg subject), volume of distribution (4.3 L/kg), oral bioavailability (40%) and transdermal bioavailability (76%) within expected ranges. The estimated fraction of the dose swallowed for buccal formulations ranged from 55% (gum) to 69% (lozenge).ConclusionsRobust population pharmacokinetic models were developed for five nicotine replacement therapy product types and for intravenous and oral nicotine. These population pharmacokinetic models are used in exposure-response analyses and simulation-based nicotine replacement therapy product design.
| S-EPMC8016787 | biostudies-literature
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| S-EPMC8804305 | biostudies-literature
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| S-EPMC8054852 | biostudies-literature
Project description:BackgroundSince the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics.MethodsThis study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias.ResultsA total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low.ConclusionsIntensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.
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| S-EPMC9000914 | biostudies-literature
Project description:BACKGROUND:Electronic nicotine delivery systems (ENDS; e-cigarettes), consisting of a battery, heating element and e-liquid, have evolved significantly with wide variation in design, components, operating powers, and chemical constituents. Generated aerosols have been reported to contain potentially toxic substances. We conducted a systematic review to assess what is known about the presence of toxicants in ENDS aerosols in order to inform how system design could mitigate risk. METHODS:Articles reporting on or evaluating design characteristics of ENDS and aerosol constituents were included and summarized. RESULTS:The search identified 2,305 articles, of which 92 were included after full-text review. Findings were grouped into 6 major categories of potentially harmful chemicals: carbonyls, volatile organic chemicals, trace elements, reactive oxygen species and free radicals, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines. In general, higher concentrations of aerosol toxicants are associated with increased power or voltage. Aerosol toxicants are also associated with e-liquid flavoring agents existing as primary ingredients or as products of thermal degradation. CONCLUSIONS:Improved ENDS design can reduce toxicant levels. Additional research is needed to develop a framework for optimizing system characteristics to minimize exposure, especially with respect to heating power and e-liquids. Both manufacturers and regulatory agencies have roles in reducing toxicants and potential health risks from ENDS.
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