Absorption, Distribution, Metabolism and Excretion of A New Iminodibenzyl Derivative Y-516 in Rats

Abstract

Absorption, distribution, metabolism and excretion of Y-516, a new psychotropic drug, were investigated in male and female rats after administration of ¹⁴C labeled compound (¹⁴C-Y-516).
When ¹⁴C-Y-516 was orally administered to rats, approximately 3.2 ?? 9.2 % and 84.9 ?? 99.8 % of ¹⁴C was excreted within 4 days in urine and feces, respectively. No sex, dose and route differences were not observed on urinary and fecal excretion. Percent recovery of ¹⁴C in bile was 62% and 75% in male and female rats, respectively.
The highest blood level of ¹⁴C was observed within 30 min after oral administration of 5 mg/kg. A good correlation was observed between blood concentrations and administered doses.
The highest concentration of ¹⁴C was found in the liver, and relatively high levels were observed in the lung, adrenal, kidney, spleen, thyroid and salivary gland. No significant accumulation of ¹⁴C was observed in any tissue except the liver 24 hours following administration. About 72% of ¹⁴C present in the serum was bound to the proteins. A little transition of ¹⁴C to the blood cell was observed.
The major metabolic pathways of Y-516 in rats are considered to be the hydroxylation at iminodibenzyl ring, and dehydrogenation at the terminal spiroamine moiety, and the hydroxylated derivatives were mainly excreted as glucuronides in the bile. No sex and dose differences were observed in metabolism of Y-516.