title: The toxicokinetic profile of curdione in pregnant SD rats and its transference in a placental barrier system detected by LC-MS/MS.
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 63 mg/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 7 mg/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 21 mg/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.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China; Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Chong
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Sichong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China; Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China. Electronic address: sunzy64@163.com.
authors.forename: Zuyue
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D018811:Maternal Exposure / Q000009:adverse effects; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D045788:Sesquiterpenes, Germacrane / Q000097:blood* / Q000633:toxicity*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D066007:Toxicokinetics
chemical_list: D045788:Sesquiterpenes, Germacrane; C504126:curdione
keywords: Curdione; Drug distribution; Toxicokinetics; Transferring capability; Vaginitis