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  • Title: Pharmacokinetics and biotransformation of diethylene glycol and ethylene glycol in the rat.
    Author: Lenk W, Löhr D, Sonnenbichler J.
    Journal: Xenobiotica; 1989 Sep; 19(9):961-79. PubMed ID: 2815837.
    Abstract:
    1. 14C-Diethylene glycol (DEG), administered orally to rats at 1, 5, and 10 ml/kg, gave elimination half-lives of 6, 6, and 10 h, respectively, from urinary excretion data. Half-logarithmic plots of urinary 14C excretion rates versus time indicated zero-order elimination for the first 9 and 18 h after oral doses of 5 and 10 ml of 14C-DEG/kg, respectively. 14C-DEG urinary elimination kinetics changed into first-order 6, 9, and 18 h after oral doses of 1, 5, and 10 ml/kg, with a half-life of 3 h. 2. After oral doses of 3 and 5 ml ethylene glycol (EG)/kg, half-lives of 4.5 and 4.1 h were estimated from cumulative urinary excretion data for non-metabolized EG. A half-life of 2 h was determined from half-logarithmic plots of urinary excretion rates of non-metabolized EG after the same oral doses of EG. 3. The urinary concentrations of non-metabolized DEG and its metabolite, 2-hydroxyethoxyacetic acid (2-HEAA), determined by high-resolution n.m.r. spectroscopy in the urine of rats doses with DEG were 61-68% and 16-31% dose, respectively. 4. Urinary concentrations of non-metabolized EG and its metabolite, glycolic acid (GA), determined by n.m.r., gave 62-67% for non-metabolized EG and 28.7% for GA following oral doses of EG. 5. Oxidation of DEG and EG in rats was accompanied by a change of urinary pH, reflecting metabolic acidosis. 6. Comparison of the KM for DEG oxidation in vitro by ADH with that of ethanol oxidation, showed a 680-fold difference in substrate affinity. DEG inhibited ethanol oxidation non-competitively, the Ki being 0.44 M.
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