Pharmacokinetics of 16-dehydropregnenolone hydroxypropyl-β-cyclodextrin inclusion complex following peroral administration

Abstract

16-Dehydropregnenolone (16-DHP) is an active compound with an unsatisfied in vivo behavior and poor water-solubility, which limits its clinical application. To improve its in vivo behavior and water-solubility, a Hydroxypropyl-beta-Cyclodextrin (HP-β-CD) inclusion complex of 16-DHP was prepared in this paper. Pharmacokinetic studies after oral administration of 16-DHP–HP-β-CD at doses of 37.5, 75, 150 mg/kg were carried out to investigate its dose proportionality in rats. The relative bioavailability was researched by comparing the area under the plasma concentration–time curve of 16-DHP–HP-β-CD and free 16-DHP after oral administration in rats at the dose of 75 mg/kg. At the same time, tissue distribution of 16-DHP–HP-β-CD after oral administration at the dose of 240 mg/kg in mice was also investigated. Consequently, 16-DHP–HP-β-CD appeared to be a linear pharmacokinetic character after peroral administration to the rat at the doses tested. Compared to free 16-DHP, inclusion complex could significantly improve the relative bioavailability (467%). Tissue distribution studies indicated that 16-DHP–HP-β-CD tended to distribute into stomach, intestine, lung, brain and liver.

Keywords:

• Bioavailability
• cyclodextrins
• distribution
• inclusions
• pharmacokinetics

We thank the Shanghai Institute of Materia Medica for donating HP-β-CD to us.

Disclosure statement

The authors report no declarations of interest.

Funding

This work was supported by the Program for Liaoning Innovative Research Team in University (No. LT 20121018) and the Project of Liaoning Distinguished Professor (2014).