Calibration and evaluation of a refined pharmacokinetic model for three homologs of phosphatidylethanol

The use of phosphatidylethanol (PEth) as a biomarker for alcohol consumption is increasing likely due to its relatively long half-life in blood. Here, we present a pharmacokinetic model for three common homologs of PEth based on concentrations of each observed in a 5-day study of daily alcohol consumption. Adult participants were 11 females and 6 males with a median age of 32 years and median BMI of 24.3, all of whom drank on 1 or more days per week with at least 1 day per month of “heavy” drinking and also free from psychiatric disorders. All participants were abstinent for one week prior to beginning the study. The overall goals of this modeling effort are the use of PEth for assessment of alcohol consumption behavior and better understanding of the biological mechanisms underlying PEth pharmacokinetics. The modeling presented encompasses both the calibration of the pharmacokinetic model from daily individual PEth measurements and the prediction of model parameters in the study population with a regression model. The overall model was then evaluated by comparison of predicted PEth levels in blood with those measured in several groups of subjects in controlled drinking experiments. The results of this modeling effort indicate that the model can predict PEth concentrations in blood from alcohol consumption albeit with high variability both between individuals and within a single individual between drinking occasions. These results suggest the possible need to refine currently used cutoffs used in clinical and forensic contexts to predict alcohol consumption amounts. (249 words).