Premium
Ethanol ‘dose‐dependent’ elimination: Michaelis‐Menten v classical kinetic analysis.
Author(s) -
Rangno RE,
Kreeft JH,
Sitar DS
Publication year - 1981
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 - 10.1111/j.1365-2125.1981.tb01287.x
Subject(s) - michaelis–menten kinetics , chemistry , volume of distribution , ethanol , elimination rate constant , pharmacokinetics , distribution (mathematics) , medicine , biochemistry , mathematics , enzyme , enzyme assay , mathematical analysis
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.