Abstract
The objective of this study was to determine the toxicokinetic profile of curdione in pregnant SD rats as well as the transference of curdione into the fetus through the placental barrier system using LC–MS/MS. Thirteen pregnant SD rats were treated with 7, 21 and 63mg/kg curdione once daily from gestational day 6 (GD6) to GD15. Blood samples were collected at different time points on GD6 and GD15. Maternal plasma, placental plasma, placenta tissue, amniotic fluid and fetal tissue were collected for concentration analysis after all the animals were sacrificed following one repeated dose on GD19. The results indicated that Cmax, AUC(0−t) and AUC(0−∞) increased in a dose-dependent manner both on GD6 and GD15. At 7mg/kg group, the total serum clearance value on GD15 was reduced to approximately 16.4% of that on GD6, and the volume of distribution was also significantly decreased (p<0.05). Curdione could be detected in the maternal plasma, placental plasma, placenta tissue, amniotic fluid and fetal tissue, and its concentration in the fetal tissue reached saturation at 21mg/kg. In conclusion, curdione presents with the risk of accumulation in pregnant SD rats and may affect the fetus via transference through the placental barrier system.
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