Within- and between-subject variations in pharmacokinetic parameters of ethanol by analysis of breath, venous blood and urine

Aims To evaluate the prerequisites for using ethanol dilution to estimate t otal body water, we studied the within and between-subject variation in the parameter estimates of a two-compartment model for ethanol pharmacokinetic s with parallel Michaelis-Menten and first-order renal elimination. Because sampling of breath might be preferable in some clinical situations the par ameter estimates derived from breath and venous blood were compared. Methods On two occasions, ethanol 0.4 g kg(-1) was given by intravenous inf usion to 16 volunteers after they had fasted overnight. The proposed model was fitted by means of nonlinear regression to concentration-time data meas ured in the breath, venous blood and urine during 360 min. The model contai ned six parameters: V-max and K-m (Michaelis-Menten elimination constants), CLd (intercompartmental distribution parameter), V-C and V-T (volumes of t he central and tissue compartment, respectively) and CLR (renal clearance). The volume of distribution, V-ss, was calculated as the sum of V-C cand V- T. Results The mean +/- total s.d. of the parameter estimates derived from blo od data were V-max 95 +/- 25 mg min(-1), K-m 27 +/- 19 mg 1(-1), CLd 809 +/ - 232 ml min(-1), V-C 14.5+/-4.31, V-T 21.2+/-4.41, CLR 3.6+/-2.0 ml min(-1 ) and V-ss 35.8+/-4.31. The variation within subjects amounted to 3%, 9%, 2 1%, 21%, 17%, 26% and 2%, respectively, of the total variation. Breath samp les were associated with a similar or lower variation than blood, both with in and between subjects. About 1.5% of the infused ethanol was recovered in the urine. Conclusions The low within-subject variation of the key parameter V-ss (onl y 2%) suggests that ethanol dilution analysed by the pharmacokinetic model applied here may be used as an index of the total body water. Breath sample s yielded at least as good reproducibility in the model parameters as venou s blood.