Disposition and metabolism of NY-198 IV. Absorption, distribution and excretion of 14c-ny-198 in rats and dogs

We studied the absorption, distribution and excretion of ¹⁴C-NY-198 in rats and dogs. In rats, ¹⁴C-NY-198 was absorbed mainly from the small intestine. In both rats and dogs, it was absorbed rapidly and completely after a single oral administration of the drug. The average whole blood levels of ¹⁴C-NY-198 in rats and dogs reached maximum concentration at 0.5 and 1 h, respectively, after an oral dose of 20 mg/kg. Peak concentrations in rats and dogs were 6.90 and 11.12 μg equivalent to NY-198/ml, respectively, and declined at half-lives of 4.80 and 6.14 h. In non-fasting rats, decrease in the fraction absorbed and delay in absorption were noted. The time-course of the whole-blood level in female rats was similar to that in male rats. Tissue levels of ¹⁴C-NY-198 in male rats were high in all tissues except the eyeball and the central nervous system compared to the whole-blood level after oral doses of 20 mg/kg. Tissue levels reached maximum 1 h after oral dosing in almost all tissues. The tissue level was highest in the kidney (11.13 μg equivalent to NY-198/g tissue). Tissue levels were less than 0.1 μg equivalent to NY-198/g or ml in all tissues 24 h after oral dosing. A tendency to accumulate was not found, judging from whole body radioautograms of rats after oral dosing. The time-course of the tissue concentrations in female rats was similar to that in male rats, showing that no sex difference exists. Serum protein binding rates were approximately 30 and 20% in rats and dogs, respectively.¹⁴C-NY-198 was mainly excreted in urine after a single oral administration of the drug to rats and dogs. Within 168 h after an oral dose of 20 mg/kg, 75.8 and 64.1% of the dose was excreted in urine, respectively. Residual components were excreted in feces via bile, and ca. 52% of the amount excreted was reabsorbed from the intestine. After repeated oral doses of 20 mg/kg of ¹⁴C-NY-198 once a day for 21 days, whole blood and tissue levels, and urinary and fecal excretion ratios were similar to those in rats after a single oral dose. In our study, no accumulation of the drug in tissue or delay in excretion was found after multiple dosing.