Developing Pharmacokinetical Model Describing Salivary Secretion of Ingested Substances

Objectives: to propose a model that analyzes the early evolution of exogenous substance concentration in the saliva. Methods: A three compartment model (mouth, digestive tract and blood)has been developed, including transfers between the compartments, and metabolic elimination. A moderate dose (0.5 g/kg) of alcohol (50% rum and 50% orange juice solution) was ingested by five healthy volunteers. Volunteers were then asked to wash the mouth with purified water directly after ingestion . Ethanol concentrations in the saliva were measured at (2.5, 5, 7.5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 150, and 180) minutes. The exchange parameters (kgs, ksb, kel) for each subject were calculated based on the values obtained using mathematical procedure (the procedure BCPOL). Validity of this model is confirmed by matching experimental data with theoretical output of the model. Results: The evolution of salivary ethanol concentrations versus time was measured; the curve had three phases (initial rapid decrease, reappearance of a salivary peak, and a slow decrease). kel was similar from one individual to another, except one whose low value maybe explained by ethnic origin (Asian). There was no explanation to the fact that ksb was related to sex, nor and for the wide variability of the parameter kgs. High correlation between experimental data and theoretical output of the model is obtained (Image). Conclusions:A minimized three-compartment model (Saliva, Gastrointestinal tube, and Blood) is able to accurately describe the dynamics of ethanol in the body,after oral administration. In this model we have a single access (saliva), this was enough to identify the parameters (kgs, ksb, kel), but this unique access will not be sufficient with a larger number of parameters were additional access in needed (blood sample for example). The number of subjects was not sufficient to estimate the predictive values of the parameters.