Pharmacokinetics of 16-dehydropregnenolone hydroxypropyl-β-cyclodextrin inclusion complex following peroral administration.
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.
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Yangyang
Y
Sun
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Lili
L
Jia
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Hui
H
Zhou
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Mengqian
M
Mao
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Xiaobo
X
Wang
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Lan
L
Wei
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Lixin
L
Sun
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D051379:Mice; D011284:Pregnenolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C003592:16-dehydropregnenolone; D011284:Pregnenolone
Bioavailability; cyclodextrins; distribution; inclusions; pharmacokinetics