title: Pharmacokinetics and tissue distribution study of 16-dehydropregnenolone liposome in female mice after intravenous administration.
abstract: OBJECTIVE
  16-Dehydropregnenolone (16-DHP) is a potential antitumor compound with poor solubility. A liposome entrapped 16-DHP (16-DHP-LM) formulation was developed to surmount its solubility obstacle. The aim of this study is to investigate the pharmacokinetics of 16-DHP-LM and 16-DHP solution in female mice and tissue distribution of 16-DHP-LM in female tumor-bearing nude mice.
  
  
  METHODS
  Rotary-evaporated film method was used to prepare 16-DHP-LM. The comparison of pharmacokinetics between 16-DHP-LM and 16-DHP solution in female mice was investigated after intravenous administration at a single dose of 15 mg/kg. The dose proportionality of 16-DHP-LM was also evaluated after intravenous administration of 16-DHP-LM at the doses of 7.5, 15.0 and 30.0 mg/kg. The tissue distribution of 16-DHP-LM in female tumor-bearing nude mice was evaluated after intravenous administration of 16-DHP-LM at a single dose of 30.0 mg/kg.
  
  
  RESULTS
  The pharmacokinetic study indicated that the 16-DHP-LM group had higher area under the plasma concentration-time curve (AUC), lower apparent volume of distribution (Vz) and smaller systemic clearance (CL) than the 16-DHP solution group. For dose proportionality, good linearity of the pharmacokinetics of 16-DHP after intravenous administration of 16-DHP-LM was observed in the regression analysis of the AUC-dose plot (r = 0.99) and the Cmax-dose plot (r = 0.98). The tissue distribution study showed that the main tissue depots for 16-DHP in tumor-bearing nude mice were plasma, liver, spleen and tumor, which was benefit to anti-tumor effect. All these results provided a significant basis for the design of clinical trial of 16-DHP-LM.
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
authors.forename: Zhenxue
authors.initials: Z
authors.lastname: Deng
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Qin
authors.affiliation: b School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
mesh_terms: D061605:Administration, Intravenous / Q000379:methods; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D007262:Infusions, Intravenous / Q000379:methods; D007275:Injections, Intravenous / Q000379:methods; D008081:Liposomes / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D019999:Pharmaceutical Solutions / Q000493:pharmacokinetics; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000502:physiology*
chemical_list: D008081:Liposomes; D019999:Pharmaceutical Solutions; C003592:16-dehydropregnenolone; D011284:Pregnenolone
keywords: 16-Dehydropregnenolone; liposome; pharmacokinetics; tissue distribution; tumor-bearing nude mouse