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

Authors


: Dr Åke Norberg, Department of Anaesthesia and Intensive Care K32, Huddinge University Hospital, S-141 86 Huddinge, Sweden. Tel.: + 46–8-58 58 00 00; Facsimile + 46 –8–779 54 24; E-mail: ake.norberg@ anaesth.hs.sll.se

Abstract

Aims  To evaluate the prerequisites for using ethanol dilution to estimate total body water, we studied the within- and between-subject variation in the parameter estimates of a two-compartment model for ethanol pharmacokinetics with parallel Michaelis-Menten and first-order renal elimination. Because sampling of breath might be preferable in some clinical situations the parameter estimates derived from breath and venous blood were compared.

Methods  On two occasions, ethanol 0.4 g kg−1 was given by intravenous infusion to 16 volunteers after they had fasted overnight. The proposed model was fitted by means of nonlinear regression to concentration-time data measured in the breath, venous blood and urine during 360 min. The model contained six parameters: Vmax and Km (Michaelis-Menten elimination constants), CLd (intercompartmental distribution parameter), VC and VT (volumes of the central and tissue compartment, respectively) and CLR (renal clearance). The volume of distribution, Vss, was calculated as the sum of VC and VT.

Results  The mean ± total s.d. of the parameter estimates derived from blood data were Vmax 95 ± 25 mg min−1, Km 27 ± 19 mg l−1, CLd 809 ± 232 ml min−1, VC 14.5 ± 4.3 l, VT 21.2 ± 4.4 l, CLR 3.6 ± 2.0 ml min−1 and Vss 35.8 ± 4.3 l. The variation within subjects amounted to 3%, 9%, 21%, 21%, 17%, 26% and 2%, respectively, of the total variation. Breath samples were associated with a similar or lower variation than blood, both within 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 Vss (only 2%) suggests that ethanol dilution analysed by the pharmacokinetic model applied here may be used as an index of the total body water. Breath samples yielded at least as good reproducibility in the model parameters as venous blood.

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