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 da ta from 100 volunteers who received placebo rt ere investigated for differe nces in routine safety laboratory parameters and vital signs between smoker s and nonsmokers. Of the 100 subjects, 47 were classified as smokers (cigar ettes only) and 53 were classified as nonsmokers. Objectives of the analysi s were to offer a basis for decision whether certain deviations of laborato ry 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 pr esent changes in laboratory values or vital signs during a trial that are d ifferent 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 bet ween smokers and nonsmokers were found for fetal leukocytes and triglycerid es (mean greater for smokers than nonsmokers), and total bilirubin (mean gr eater 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 res pective values during the trials. Prospective studies with sufficient large sample sizes are required to confirm the results of this retrospective ana lysis on a wider basis, and to possibly achieve significance for further di fferences between smokers and nonsmokers. (C) 1998 The American College of Clinical Pharmacology.