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The pharmacokinetics of glycyrrhetic acid (GLA) was examined in rats after bolus i.v. injection at a dose of 2, 5, or 12 mg/kg. The decline in plasma concentration was generally biexponential at each dose, but the terminal disposition became much slower with increase of dose. A greater than proportional increase in plasma GLA concentration was observed with increase of dose, suggesting a dose-dependency of GLA disposition. Apparent total body clearance decreased significantly with increase of dose. On the other hand, the apparent steady-state distribution volume after i.v. administration was unaffected by dose. The plasma disposition at each dose fitted well to a two-compartment pharmacokinetic model with Michaelis-Menten elimination. It was concluded that the pharmacokinetics of GLA in the rat is dose-dependent owing to a saturable elimination rate. The plasma level of GLA after glycyrrhizin (GLZ) i.v. dosing (100 mg/kg) in the control rats (without biliary fistulization) sustained the concentration range of 1.5-3 micrograms/ml during 1-48 h, but that in the rats with biliary fistulization declined with time. It was suggested that the sustained plasma level of GLA is accounted for by the intestinal reabsorption of GLA produced from GLZ and GLA-conjugates during the enterohepatic recycling of both.

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The mannan of bakers' yeast (Saccharomyces cerevisiae) was fractionated on a column of diethylaminoethyl-Sephadex into five subfractions. Phosphate content of these mannan subfractions was proportional to the concentration of NaCl solutions used in the chromatographic separation. Quantitative precipitin reactions showed that the serological reactivities of the subfractions were proportional to the content of phosphate. The result of acetolysis study showed that the amounts of mannotetraose and phosphate-containing oligosaccharide fractions increased proportionally to the acidity, whereas the amount of mannose decreased inversely. The results from quantitative precipitin reaction tests and acetolysis study demonstrated that both phosphate contents and multiplicity of branching moieties of mannan subfractions increased proportionally, i.e., micro-heterogeneity concerning the acidity comprised in the parent bulk mannan is not attributable merely to the coexistence of molecular species containing different amounts of phosphate but also to the presence of more of the branching moieties.

No abstract