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Introduction Tobacco harm reduction aims to provide reduced risk alternatives to adult smokers who would otherwise continue smoking combustible cigarettes (CCs). This randomized, open-label, three-arm, parallel-group, single-center, short-term confinement study aimed to investigate the effects of exposure to selected harmful and potentially harmful constituents (HPHCs) of cigarette smoke in adult smokers who switched to a carbon-heated tobacco product (CHTP) compared with adult smokers who continued to smoke CCs and those who abstained from smoking for 5 days. Methods Biomarkers of exposure to HPHCs, including nicotine and urinary excretion of mutagenic material, were measured in 24-hour urine and blood samples in 112 male and female Caucasian smokers switching from CCs to the CHTP ad libitum use. Puffing topography was assessed during product use. Results Switching to the CHTP or smoking abstinence (SA) resulted in marked decreases from baseline to Day 5 in all biomarkers of exposure measured, including carboxyhemoglobin (43% and 55% decrease in the CHTP and SA groups, respectively). The urinary excretion of mutagenic material was also markedly decreased on Day 5 compared with baseline (89% and 87% decrease in the CHTP and SA groups, respectively). No changes in biomarkers of exposure to HPHCs or urinary mutagenic material were observed between baseline and Day 5 in the CC group. Conclusions Our results provide clear evidence supporting a reduction in the level of exposure to HPHCs of tobacco smoke in smokers who switch to CHTP under controlled conditions, similar to that observed in SA. Implications The reductions observed in biomarkers of exposure to HPHCs of tobacco smoke in this short-term study could potentially also reduce the incidence of cancer, cardiovascular and respiratory diseases in those smokers who switch to a heated tobacco product.

We performed a cross-sectional, multicentre study in Japan to detect the differences in biomarkers of exposure and cardiovascular biomarkers between smokers and non-smokers. Several clinically relevant cardiovascular biomarkers differed significantly between smokers and non-smokers, including lipid metabolism (high-density lipoprotein cholesterol concentrations – lower in smokers), inflammation (fibrinogen and white blood cell count – both higher in smokers), oxidative stress (8-epi-prostaglandin F2α – higher in smokers) and platelet activation (11-dehydro-thromboxane B2 – higher in smokers) (p ≤ 0.0001). These results provide further evidence showing that cardiovascular biomarkers can discriminate smokers from non-smokers, and could be used to evaluate the risks associated with tobacco products.

This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; N = 79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N = 237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.

A randomised, double-blind, single-centre, vehicle-controlled clinical trial was conducted to assess the efficacy and tolerability of diclofenac-Na 0.1% gel in 172 subjects suffering from acute first-degree natural sunburn. Overall 172 subjects with skin phototypes II-IV were randomised in a ratio of 2:1 to receive two applications of either diclofenac-Na 0.1% Emulgel gel or its vehicle Emulgel gel, 6 and 10 hours after the end of sun exposure. Subjects were drawn from a target population of healthy volunteers and well outdoor sunbathers with normal tolerance to ultraviolet light and the sun. Previously untanned areas were exposed to carefully determined standardised doses of sun (2.8 individual minimal erythema doses) on 15% body surface area to induce first-degree sunburn. After administration of diclofenac-Na 0.1% gel, subjects reported a significant reduction in spontaneous pain intensity compared with those on vehicle. Pain relief was rapid with a reduction in erythema, which was apparent within the first few hours after the first application of the trial medication with a maximum effect observed up to 30 hours after sun exposure. A good', very good', or excellent' cooling effect was recorded by 85% of subjects after treatment. Reported treatment-emergent adverse effects were infrequent, generally mild and none were considered to be related to the trial medication. Only one severe treatment emergent adverse event (abdominal pain) was recorded in the active group, and another (burning sensation) with vehicle.

Population and family studies were undertaken to validate caffeine as a probe drug to establish the genetic status of rapid acetylators and slow acetylators. The acetylator status was established from the urinary metabolic ratio of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine (AFMU/1X) after oral administration of caffeine. We confirmed a bimodal distribution (X21 = 229.48; p « 10 −9) of the AFMU/1X ratio in 245 unrelated subjects. A third distribution did not significantly improve the fit to the data (X21 ≪ 0.04; p = 0.84). Complex segregation analysis of 76 nuclear families confirmed the monogenic inheritance of N-acetyltransferase, with incomplete dominance of the rapid allele over the slow one. We observed a slight shift between the mean activities of heterozygous and homozygous rapid acetylators (t = 2.89; p < 0.01). However, the 30 obligate heterozygotes belonging to the 76 families were evenly distributed among the rapid acetylators and never located in a hypothetic intermediary group between slow acetylators and rapid acetylators. Clinical Pharmacology and Therapeutics (1993) 54, 134–141; doi:10.1038/clpt.1993.124