Ideally a pharmacokinetic model determined following one dose of ethanol should be able to predict blood concentrations following administration of a different dose or a dose infused over a longer or shorter period of time. Previously constructed models developed for men do not do this. In this project, a dose of ethanol will be administered to the same individual over three different time periods on three separate days. Both men and women will be studied. Pharmacokinetic analysis will be performed to determine the suitability of a 2 compartment open model with dual elimination pathways to fit blood alcohol concentrations obtained following all three times of infusion. Initial pharmacokinetic analysis reveals that distribution of ethanol is saturable. Following rapid infusions, blood alcohol concentrations drop 30% in the 15 min following the cessation of the infusion; there is no similar drop when the infusion rate is slower. The size of the smaller compartment is approximately 20% of total body water. Peak blood alcohol concentration is very dependent on a subjects total body water. When ethanol is dosed as g/L total body water, peak concentrations are similar in men and women. Dual elimination pathways are necessary to adequately model concentrations 15-45 min post- infusion. A single elimination pathway can adequately predict terminal concentrations with loss of fit at the early post-infusion times. Elimination and distribution parameters are similar in men and women. - pharmacokinetics, alcohol, men, women, modeling, beta-hydroxybutyrate, acetoacetate - Human Subjects
