Abstract

Objective: To develop a method for evaluating the carcinogen delivery of potential reduced exposure products (PREPs) like Advance™, a PREP marketed to reduce smokers’ exposure to one tobacco specific nitrosamine (TSN), NNK, a potent lung carcinogen.

Design, setting, and participants: Latin square ordered, three condition, outpatient, crossover design with 12 smokers of light or ultra-light cigarettes (15 or more cigarettes/day). In each five day condition, participants either smoked own brand, Advance™, or no cigarettes. Also, on the first and last day of each condition, participants smoked one cigarette in the laboratory.

Main outcome measures: Subject rated measures of tobacco/nicotine withdrawal, expired air carbon monoxide, urine concentrations of cotinine and NNAL (one TSN biomarker), puff volume, duration, number, and interpuff interval.

Results: Relative to own brand, Advance™ produced similar withdrawal suppression, slightly lower carbon monoxide, equivalent cotinine, and 51% lower NNAL concentrations. The lowest cotinine and NNAL concentrations were observed in the no cigarette condition. Participants took fewer puffs when smoking Advance™.

Conclusions: Past experience with PREPs that failed to reduce smoking’s harm demonstrates the need for clinical methods in PREP evaluation. This study shows how assessing PREP induced changes in withdrawal and exposure to carbon monoxide, nicotine, and carcinogens may help predict PREP harm reduction potential. Adequate withdrawal suppression, slightly lower concentrations of carbon monoxide, and reduction of one TSN biomarker were observed for Advance™. In the future, clinical methods like those described here may be valuable for evaluating PREPs before they are marketed publicly.