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Within‐ and between‐subject variations in pharmacokinetic parameters of ethanol by analysis of breath, venous blood and urine
Author(s) -
Norberg Å.,
Gabrielsson J.,
Jones A. W.,
Hahn R. G.
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00194.x
Subject(s) - pharmacokinetics , venous blood , urine , chemistry , volume of distribution , elimination rate constant , distribution (mathematics) , blood volume , chromatography , anesthesia , medicine , mathematics , biochemistry , mathematical analysis
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: V max and K m (Michaelis‐Menten elimination constants), CL d (intercompartmental distribution parameter), V C and V T (volumes of the central and tissue compartment, respectively) and CL R (renal clearance). The volume of distribution, V ss , was calculated as the sum of V C and V T . Results The mean ± total s.d. of the parameter estimates derived from blood data were V max 95 ± 25 mg min −1 , K m 27 ± 19 mg l −1 , CL d 809 ± 232 ml min −1 , V C 14.5 ± 4.3 l, V T 21.2 ± 4.4 l, CL R 3.6 ± 2.0 ml min −1 and V ss 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 V ss (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.