Pharmacokinetics and tissue distribution study of 16-dehydropregnenolone liposome in female mice after intravenous administration

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 C_max-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.

16-Dehydropregnenolone; liposome; pharmacokinetics; tissue distribution; tumor-bearing nude mouse.