Inter- and intra-individual variability of ethanol pharmacokinetics over a long period of time

In most research, the inter- and intra-individual variability of time profiles of ethanol concentration has been studied over a relatively short period of time. We present a study of inter- and intra-individual variability of ethanol pharmacokinetics in five healthy volunteers (social drinkers) over a period of around eight years. The volunteers received a dose of 0.7 g/kg (men) and 0.6 g/kg (women) of ethanol in the form of vodka diluted with mineral water. The blood ethanol concentrations in a series of samples were measured by gas chromatography. For pharmacokinetic calculations, a model with first-order absorption and Michaelis-Menten elimination was applied. A linear regression technique was used to calculate Widmark's coefficient. The area under the concentration-time curve (AUC) was calculated by trapezoid rule. A tendency for pharmacokinetic parameters to alter during the study time was observed, however, these changes were random and did not correlate with the duration of the study. The highest inter- and intra-subject variability of the half time of absorption was observed. The maximal elimination velocity and Michaelis-Menten constant were also very unstable; coefficients of variation were 55.8% and 79.0%, respectively. Other calculated pharmacokinetic parameters (AUC, beta60, V/F, Cmax) were characterized by a lower variability with a coefficient of variation around 36%. Back extrapolation of plasma ethanol concentration using mean value of beta60 for each subject showed that results could be underestimated up to 26% or overestimated up to 102%.