安息香酸のナトリウム塩及びカリウム塩のラットにおける体内動態

抄録

The absorption, disposition, metabolism and excretion of sodium [¹⁴C]-benzoate (NaBA) and potassium [¹⁴C]-benzoate (KBA) was studied after oral administration of low (BA 25.4mg eq/kg), middle (BA 254mg eq/kg), and high (BA 1050mg eq/kg) dosages to male Wistar rats. Excretion of [¹⁴C]-BA derived radioactivity was monitored in the urine and feces, and as exhaled [¹⁴CO₂] from 0 to 48h. The tissue distribution of the radioactivity of NaBA was similar to that of KBA. At 6h after administration, more than a half of the radioactivity remained in rat at high dosage and 3-7% of the radioactivity remained in rats at low and middle dosages of NaBA and KBA. Relatively high concentration of the radioactivity remained in the stomach, intestine, kidney and liver. At 48h after administration, less than 0.7% of the radioactivity remained in rat at low, middle and high dosages of NaBA and KBA. At all dosages of NaBA and KBA, more than 96.8% of the radioactivity was excreted in the urine within 48h and that by the other routes were very low. The major urinary metabolite of BA was hippuric acid (HA). The higher doses of BA has delayed T_max and the urinary excretion, and increased C_max and the concentration of BA in the serum. AUC and tissue distribution were not linearly related to the administered dose. The dose effects of BA suggest the saturation of elimination, probably caused by the saturation of the metabolic pathway of BA to HA over middle dosage. Blood levels of the radioactivity monitored during 48h were applied to one compartment model with the first-order absorption and Michaelis-Menten elimination. There was no significant difference between NaBA and KBA in the absorption, distribution, metabolism and excretion.