title: Different pharmacokinetics of the two structurally similar dammarane sapogenins, protopanaxatriol and protopanaxadiol, in rats.
abstract: Dammarane Sapogenins (DS), with main ingredients of protopanaxatriol (PPT, 33%) and protopanaxadiol (PPD, 16%), is an alkaline hydrolyzed product of ginsenosides and had significant activities in improving learning and memory and decreasing chemotherapy-induced myelosuppression. In the present study, the pharmacokinetics and oral bioavailabilities of PPT and PPD were investigated when a single dose of DS was administrated orally (75 mg/kg) and intravenously (i.v., 30 mg/kg) to rats. Their in vitro stabilities in the GI tract were also investigated. PPT and PPD concentrations were measured by LC-MS. The results showed that PPT was eliminated rapidly from the body with an average t1/2, λz value of 0.80 h and CL of 4.27 l/h/kg after i.v. administration, while PPD was eliminated relatively slowly with a t1/2, λz of 6.25 h and CL of 0.98l/h/kg. After oral administration, both PPD and PPT could be absorbed into the body, but their systemic exposures were quite different. PPT was absorbed into the body quickly, with a Tmax of 0.58 h and a Cmax of 0.13 μg/ml, while PPD was absorbed relatively slowly with a Tmax of 1.82 h and a Cmax of 1.04 μg/ml. The absolute bioavailabilities of PPT and PPD were estimated as 3.69% and 48.12%, respectively. The stability test found that PPT was instable in the stomach with 40% degradation after 4h incubation at 37°C, both in pH1.2 buffer and in the stomach content solution. The instability in the stomach might be one of the reasons for PPT's poor bioavailability.
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
authors: Ling-Ti
authors: LT
authors: Kong
authors: Qian
authors: Q
authors: Wang
authors: Bing-Xin
authors: BX
authors: Xiao
authors: Yong-Hong
authors: YH
authors: Liao
authors: Xiao-Xi
authors: XX
authors: He
authors: Lin-Hu
authors: LH
authors: Ye
authors: Xin-Min
authors: XM
authors: Liu
authors: Qi
authors: Q
authors: Chang
mesh_terms: D000818:Animals; D001682:Biological Availability; D004333:Drug Administration Routes; D005753:Gastric Mucosa / Q000378:metabolism*; D005766:Gastrointestinal Contents; D036145:Ginsenosides / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D015394:Molecular Structure; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D036145:Ginsenosides; D010936:Plant Extracts; D012502:Sapogenins; C081552:protopanaxatriol; C062916:protopanaxadiol