Laboratory values and vital signs in male smokers and nonsmokers in phase I trials: a retrospective comparison

In a retrospective analysis of 13 phase I multiple-dose trials, clinical data from 100 volunteers who received placebo were investigated for differences in routine safety laboratory parameters and vital signs between smokers and nonsmokers. Of the 100 subjects, 47 were classified as smokers (cigarettes only) and 53 were classified as nonsmokers. Objectives of the analysis were to offer a basis for decision whether certain deviations of laboratory values or vital signs might be related to smoking rather than to a study drug or some external influence, and to explore whether smokers tend to present changes in laboratory values or vital signs during a trial that are different from changes that occur in nonsmokers. Regarding baseline values, which were defined as the mean of values at screening and the first day of the in-house stay, clinically and statistically significant differences between smokers and nonsmokers were found for total leukocytes and triglycerides (mean greater for smokers than nonsmokers), and total bilirubin (mean greater for nonsmokers than smokers). Comparison of changes during the study in smokers and nonsmokers showed a statistically and clinically significant difference only for triglyceride levels. Smokers had a slight decrease in triglyceride levels, whereas nonsmokers showed a marked increase in the respective values during the trials. Prospective studies with sufficiently large sample sizes are required to confirm the results of this retrospective analysis on a wider basis, and to possibly achieve significance for further differences between smokers and nonsmokers.