DEVELOPMENT AND APPLICATION OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR ETHANOL IN THE MOUSE

The purpose of the present study was to develop a physiologically base d pharmacokinetic (PBPK) model in the mouse and to utilize it to evalu ate the relative contribution, if any, of gastric alcohol dehydrogenas e (ADH) to the bioavailability of ethanol. The PBPK model developed in Swiss Webster male mice accurately simulated blood and brain ethanol concentrations following an intraperitoneal administration of 0.82 and 3.2 g of ethanol/kg body weight. Application of the model illustrated that inclusion of gastric ADH into the model provided a less accurate fit to the experimental data, and therefore gastric ADH did not contr ibute to the overall disposition of an orally administered ethanol dos e of 0.75 g/kg. Furthermore, the model also indicated that changes in percentage cardiac output to the liver had a minimal effect on the blo od ethanol concentration (BEC) time curve. The results illustrate the validity of the PBPK model developed for ethanol and demonstrate that in the Swiss Webster male mouse the bioavailability of ethanol is mini mally affected, if at all, by metabolism by gastric ADH.