Correlation and predictive performances of saliva and plasma nicotine concentration on tobacco withdrawal-induced craving

Aims To investigate whether saliva is a useful alternative to plasma for routine monitoring of nicotine and evaluate the predictive performances of saliva and plasma concentration on craving estimated by a Tiffany Questionnaire on Smoking Urge-Brief Form. Methods Thirteen healthy smokers were enrolled in a randomized, two period, crossover trial. Linear and power models were evaluated to predict the plasma nicotine concentrations from the saliva measurements, whereas a population PK/PD indirect response model was used to predict craving using either saliva or plasma nicotine concentration as the independent variable. Results The results of the analysis revealed that the power model was preferred over the linear one The bias on the predicted plasma concentrations was of 0.47 ng ml(-1) with a 95% confidence interval of [- 0.57, 1.52] and a precision of 5.68 ng ml(-1). The placebo effect model was initially fitted to data, then the indirect response approach (with inhibition in kin) was used to model the craving scores using plasma and saliva nicotine concentrations as independent variables. The two indirect response PK/PD models based on saliva and plasma nicotine concentrations, adequately described the onset, extent, and duration of craving. The maximal inhibition I-max was 0.722 and 1 for saliva and plasma concentrations while the estimated nicotine concentrations giving 50% of the maximal inhibition were 269 ng ml(-1) and 24.3 ng ml(-1) for saliva and plasma, respectively. Conclusions A good correlation between plasma and saliva nicotine concentrations has been found using a power model. Comparable values of bias and precision on the model-predicted craving indicate that plasma and saliva concentration can equally well be used to predict the onset of tobacco withdrawal induced craving. Analysis of saliva definitely offers a potentially more attractive way to assess nicotine concentration values, as samples can be collected easily and noninvasively. In addition, saliva sampling avoids the pain and discomfort involved in venepuncture. In studies that assess psychological measures, such as subjective mood, blood collection could present a possible confounding factor because of the anxiety and pain that accompanies it. For these reasons saliva can reasonably be considered as the ideal sampling site for all clinical studies conducted for the evaluation of the potential activity of drugs on nicotine deprivation symptoms.