The importance of measuring cotinine levels to identify smokers in clinical trials

Abstract

First-time-in-humans studies of drugs (phase I) typically exclude unsuitable volunteers by testing for recreational drugs. However, volunteers are usually not screened for cotinine, a metabolite of nicotine, even though tobacco products may alter pharmacokinetic and pharmacodynamic parameters and withdrawal from tobacco may cause additional adverse events. The accuracy of personal histories as a means of excluding smokers was examined prospectively in three phase I units in the northeastern, midwestern, and southwestern United States. In studies intended for nonsmokers, 45 of 282 purported nonsmokers screened before enrollment tested positive for cotinine. This suggests that personal histories are unreliable in determining tobacco use in clinical trials designated for nonsmokers.

Urinary cotinine as a tobacco-smoke exposure index: a minireview

“…However, these authors indicate that cotinine levels are lower than 80 ng/ml urine in the majority of nonsmokers [25] or that a threshold value of 50 ng/ml urine would have been more appropriate [1].…”

“…Curiously, higher thresholds of 500 [1,25] and 1000 ng/ml urine or mg creatinine [48] have been proposed when urinary determination is based on a¯uorescence polarization immuno-assay (FPIA). However, these authors indicate that cotinine levels are lower than 80 ng/ml urine in the majority of nonsmokers [25] or that a threshold value of 50 ng/ml urine would have been more appropriate [1].…”

Serum proteomic analysis during nicotine self‐administration, extinction and relapse in rats

“…Changes induced by nicotine exposure on peripheral cells may be correlated to the changes observed in brain [15,16]. Reliable peripheral biomarkers are needed to evaluate smoking habits objectively, since self-reports may be misleading [17]. Cotinine, the major nicotine metabolite, or carbon monoxide are used as biomarkers for tobacco smoking [18], but the availability of other biomarkers of nicotine dependence would be helpful [19].…”

Recruiting Healthy Volunteers for Research Participation via Internet Advertising

“…Database recruiting advertisements can emphasize compensation and other benefits not only via the verbiage chosen, but also by text appearance (e.g., bold face type, block capitalization, italics), and this creates the potential for volunteers to focus on the benefits and underestimate or dismiss the risk of harm that can directly result from participation. 20,21 In addition to the clinical impact, personal financial impact can be significant for the uninsured or underinsured as most studies do not provide free medical care to treat adverse events resulting from study participation. 16 medical center be given a guaranteed $20 and a chance to win more money (on average $6)."…”