Pharmacokinetic Studies of 3-Methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) in Rats (3): Feto-Placental Transfer and Excretio n into Milk

Abstract

Feto-placental transfer and excretion into milk were investigated in pregnant and nursing female rats after a single intravenous administration of ¹⁴C-MCI-186 (2 mg/kg).
1) In pregnant rats, on day 14 of gestation, the level of radioactivity in fetus was 0.56 μg/g at 5 min after administration, that was low at 1/23 of the maternal plasma concentration, then decreased rapidly.
2) In pregnant rats, on day 19 of gestation, the level of radioactivity in fetus was 0.91 μg/g at 5 min after administration, that was 1/9.9 of the maternal plasma concentration, and the transfer rate to fetus increased by increasing the gestation days. In fetus, the levels of radioactivity in intestine, kidney, liver and brain showed high levels in the order. About 44% and 23% of the radioactivity in fetus consisted of sulfate and glucuronide of MCI-186, respectively. Glucuronide was transfered to fetus more easily than sulfate. Decrease of radioactivity from fetus, especially from fetal intestine, was delayed, therefore concentration of radioactivity in fetus at 24 hr after administration was 2 times higher than that in maternal plasma.
3) Concentrations of radioactivity in the milk reached maximum (0.71 μg/ml, at 15 min after administration. Milk concentrations decreased more slowly than plasma concentrations, and ratios of milk to plasma concentrations increased parallel with course of time. The radioactivity in the milk consisted mainly of MCI-186 sulfate.