Abstract
Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were administered to rats, either in the form of Sanqi extract or as pure chemicals. The ginsenosides Ra3, Rb1, Rd, Re, Rg1, and notoginsenoside R1 were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra3, Rb1, and Rd after oral administration of the extract was significantly greater than that to the other compounds. Considerable colonic deglycosylation of the ginsenosides occurred, but the plasma levels of deglycosylated metabolites were low in rats. Poor membrane permeability and active biliary excretion are the two primary factors limiting systemic exposure to most ginsenosides and their deglycosylated metabolites. In contrast with other ginsenosides, biliary excretion of ginsenosides Ra3 and Rb1 was passive. Meanwhile, the active biliary excretion of ginsenoside Rd was significantly slower than that of other saponins. Slow biliary excretion, inefficient metabolism, and slow renal excretion resulted in long-circulating and thus relatively high exposure levels for these three ginsenosides. For these reasons, plasma ginsenosides Ra3, Rb1, and Rd were identified as pharmacokinetic markers for indicating rat systemic exposure to Sanqi extract. This is a systematic investigation of the absorption and disposition of ginsenosides from an herb, the information gained from which is important for linking Sanqi administration to its medicinal effects.
Footnotes
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This work was supported in part by the National Basic Research Program of China [Grant 2005CB523403]; the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” [Grant 2009ZX09304-002]; the National Science Fund of China for Distinguished Young Scholars [Grant 30925044]; the National Natural Science Foundation of China [Grant 90209044]; and the Shanghai Science and Technology Major Project [Grant 08DZ1980200].
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.109.029819
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- ppd-type
- 20(S)-protopanaxadiol type
- ppt-type
- 20(S)-protopanaxatriol type
- PK
- pharmacokinetic
- GRb1
- ginsenoside Rb1
- GRd
- ginsenoside Rd
- GRg3
- ginsenoside Rg3
- GF2
- ginsenoside F2
- GRh2
- ginsenoside Rh2
- GRe
- ginsenoside Re
- GRg1
- ginsenoside Rg1
- GRf
- ginsenoside Rf
- GF1
- ginsenoside F1
- NGR1
- notoginsenoside R1
- C-K
- compound-K
- Ppd
- protopanaxadiol
- Ppt
- protopanaxatriol
- GRa3
- ginsenoside Ra3
- GRc
- ginsenoside Rc
- 20gRf
- 20-gluco-ginsenoside Rf
- GRh1
- ginsenoside Rh1
- GRg2
- ginsenoside Rg2
- MK571
- 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid
- AUC
- area under concentration-time curve
- CLB
- biliary clearance
- CLR
- renal clearance
- Cum.Ae
- cumulative amount excreted during sampling period
- Papp
- apparent permeability coefficient
- P-gp
- P-glycoprotein
- MRP2
- multidrug resistance-associated protein 2
- S
- aqueous solubility at a given pH
- TPSA
- topological polar surface area
- LC
- liquid chromatography
- t1/2
- elimination half-life
- CLtot,p
- total plasma clearance
- QSPKR
- quantitative structure-PK relationships.
- Received August 5, 2009.
- Accepted September 23, 2009.
- Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics
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