Article date: November 1981
By: RE Rangno, JH Kreeft, DS Sitar, in Volume 12, Issue 5, pages 667-673
1 To compare classical linear regression techniques and a Michaelis‐ Menten elimination model eight normal human volunteers each received three intravenous doses (0.375, 0.5, and 0.75 g/kg) of ethanol and four of the subjects each received four oral doses (0.5, 0.65, 0.95, 1.25 g/kg) of ethanol. 2 Computerized analysis of the time‐plasma concentration profiles using a two‐compartment Michaelis‐Menton elimination model yielded a median absorption constant of 1.29 h‐1; volume of distribution of 0.47 l/kg; Vmax of 0.12 g h‐1 kg‐1; and Km of 0.03 g/l. Classical techniques resulted in a slope of 0.20 g l‐1 h‐1, volume of distribution of 0.55 l/kg, and a B60 of 0.11 g h‐1 kg‐1. 3 Transient post‐prandial decreases in elimination slope occurred at higher oral doses. A trend of increasing slope with increasing oral dose was seen at concentrations well above the Km. Time to sobriety (0.8 g/l) increased nonlinearly with increasing peak concentration. 4 Maximal ethanol elimination rates are determined equally well by the two techniques. Classical analyses overestimate the volume of distribution of ethanol by 17%. Neither technique helps explain the post‐prandial changes in slope or increasing slope with dose at high concentrations.
DOI: 10.1111/j.1365-2125.1981.tb01287.x
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