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.