¹⁴C-PC-904のラットにおける体内動態について

抄録

The biological disposition and metabolic fate of PC-904, sodium (2 S, 5 R, 6 R)-6-[(R)-2-(4-hydroxy-1, 5-naphthyridine-3-carboxamido)-2-phenylacetamido]-3, 3-dimethy1-7-oxo-4-thia-l-azabicyclo [3. 2. 0] heptane-2-carboxylate, were studied in rats after intravenous injection of ¹⁴C-PC-904.
1) Plasma levels of ¹⁴C rapidly decreased with a biological half life of about 20 minutes until 3 hours after injection (50 mg/kg), then gradually decreased.
2) The liver, kidneys and blood showed the highest ¹⁴C levels, while the brain and the spinal cord showed the lowest levels.
3) A dose response in the tissue levels of ¹⁴C was observed 1 hour after injection when the dose was raised (12. 5, 50 and 200 mg/kg).
4) Both male and female rats excreted about 80% and 20% of the ¹⁴C dose in the feces and urine, respectively, in 72 hours after injection (50 mg/kg).
5) Biliary excretion of ¹⁴C decreased (72 to 38%) when the dose was raised (50 to 800 mg/kg), while the urinary excretion increased 22 to 55% of the ¹⁴C dose, the total ¹⁴C excretion being unchanged. About 83% of the dose was excreted in the urine in bile-duct ligated rats within 24 hours after injection of ¹⁴C-PC-904 (50 mg/kg).
6) Tissue distribution of ¹⁴C in pregnant rats showed much lower levels of ¹⁴C in fetuses than that in the dams that showed a similar pattern of ¹⁴C distribution to male rats.
7) Analyses by HLC revealed that most of the ¹⁴C in the urine and bile was unchanged PC-904.