Equilibration, distribution, and elimination of a single dose of intravenous ethanol in dogs with intact renal function or anuria.

We infused 11 mmol/kg of intravenous ethanol into dogs with either intact renal function (n = 5) or ureteral ligation (n = 7), and studied by frequent blood sampling and by urine collection the time and mode of ethanol equilibration, the elimination parameters, and the comparison of observed equilibrated plasma ethanol levels to levels predicted either by linear or by nonlinear kinetics. Equilibration time was 25 min or less, renal fraction of elimination was less than 5% of total elimination, and both linear (elimination rate) and nonlinear (Vmax and Km) elimination parameters were not different between dogs with intact renal function and dogs with anuria. Serum sodium concentration did not change throughout the experiments, eliminating the hypothesis that acute ethanol load creates clinically significant temporary osmotic water transfer from the intracellular into the extracellular compartment. Distribution volumes of ethanol from linear kinetics were slightly, but not statistically, greater than volumes from nonlinear kinetics. Equilibrated plasma ethanol levels predicted by linear kinetics agreed closely with observed levels greater than 4 mmol/liter, but underestimated observed levels less than 4 mmol/liter. Equilibrated plasma ethanol levels predicted by nonlinear kinetics agreed with observed levels throughout the range of observed concentrations. The use of linear kinetics to predict blood ethanol levels should be limited to the pseudolinear portion of the blood alcohol curve.

Pharmacokinetic study of methyl glyoxal-bis-guanylhydrazone (methyl-GAG).

Using a paired ion exchange high pressure liquid chromatographic assay, pharmacokinetic evaluation of methyl glyoxal bis guanylhydrazone (methyl-GAG) was performed in nine male New Zealand albino rabbits following administration of a single intravenous bolus dose of 50 mg/kg B.W (550 mg/m2 BSA). Blood samples were collected before and at intervals of 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after administration of the drug. The analysis of experimental data indicates a three compartment open model with first order elimination from the central compartment described by the equation Cpt = A.e-alpha t + B.e-beta t + C.e-gamma t, where A, B, C, are 107.985, 4.785, and 0.763 micrograms/ml, respectively. alpha, beta, gamma, are 5.466, 0.487, and 0.030 h-1, respectively, and T1/2 alpha, beta, gamma are 7.6, 85.3 min and 23.1 h, respectively. The mean volume of distribution in the central compartment Vc was 0.44 liters (1)/kg, volume of distribution Vdarea 30.326 1/kg, and the total body clearance 0.9097 1/kg/h. The existence of a long terminal plasma half life of methyl-GAG reported previously in human studies was also confirmed in experimental animals and may explain the cumulative toxicity of this drug.