Metabolic Fate of YNK01(3): Fetoplacental transfer and excretion into milk after Single Administration of [¹⁴C]YNK01 to Rats

Abstract

Fetoplacental transfer and excretion into the milk were studied in rats after oral administration of [¹⁴C] 4-amino-1-β-D-arabinofuranosyl-2 (1H)-pyrimidinone 5'-(sodium octadecyl phosphate) monohydrate (YNK01) at 25mg/kg.
1. After oral administration of [¹⁴C]YNK01 to fasting pregnant rats at 25mg/kg, the radioactivity transferred to fetuses was comparable to that in maternal plasma on 18th day of gestation. Similarly as in the case of mothers, radioactivity disappeared slowly from the fetal brain, eyeball, thymus, skin, etc. Whole body autoradiograms revealed that transfer of radioactivity to fetuses on the 12th day of gestation was of a low level compared to that on 18th day.
2. After oral administrati on of [¹⁴C]YNK01 to non-fasting lactating rats at 25mg/kg on 10th day after delivery, the concentration in milk increased with time, reaching maximum at 8 hours after dosing, and decreased to the levels below the detection limit at 48 hours. Although the plasma concentration was higher in the early stage after dosing, milk-to-plasma concentration ratio rose with time, reaching 1.48 at 24 hours after dosing. Subsequently, radioactivity in milk decreased to the levels below the detection limit.