Intra- and inter-individual variability in urinary nicotine excretion and plasma cotinine in adult cigarette smokers

Urinary nicotine equivalents (NE) and plasma cotinine are widely used as a biomarker for exposure to tobacco products, but there is limited information on intra- and inter-individual variability in the literature. Data were gathered from 13 randomized controlled clinical studies sponsored by Philip Morris USA, with study durations between 2 and 8 days for the short term (ST) and 3–12 months for the long term (LT) studies. Coefficients of variation (CV) were compared and a linear mixed model was used to partition the total study variability into inter- and intra-individual variability. In the ST and LT studies respectively, the root–mean–square (RMS) intra-individual CV was 19% and 29% for NE (mg/24 h); 19% and 33% for NE (mg/cig) and 13% and 22% for plasma cotinine. The RSM inter-individual CV was 38% and 38% for NE (mg/24 h), 25% and 32% for NE (mg/cig) and 38% and 37% for plasma cotinine, in ST and LT study, respectively. Intra-individual CV was smaller in ST studies than in LT studies, and was significantly less than inter-individual CV in ST studies. Daily cigarette consumption alone could not explain all the variability in NE and plasma cotinine. The variability estimates could be used for clinical study design of clinical and developing regulatory guidance.