Metabolism and pharmacokinetic study of ardipusilloside I in rats.
Ardipusilloside I, extracted from  ARDISIA PUSILLA A.DC, effectively inhibits the progression of several cancers in animal models and is a potential anti-cancer drug candidate. However, the metabolism and pharmacokinetic characteristics of ardipusilloside I remain unknown. In this study, we developed a highly sensitive liquid chromatography-tandem MS method to determine the ardipusilloside I concentration in rat plasma using ginsenoside Re (whose structure is similar to ardipusilloside I) as the internal standard. After oral administration of ardipusilloside I, its four possible metabolites (M1, M2, M3, and M4, whose structures were determined by MS) were detected in the content from rat small intestine. In rat plasma, however, only M3 and M4 were detected after oral administration of ardipusilloside I. None of the metabolites were detected in plasma samples after intravenous administration of ardipusilloside I to rats. These results indicated that the metabolites, but not the drug itself, were absorbed into plasma after oral administration of ardipusilloside I to rats and that M3 and M4 may be responsible for the antitumor activity of orally administered ardipusilloside I in rat models of cancer.
Department of Pharmacy, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Xiao-Juan
XJ
Wang
Han
H
Cui
Rong
R
Wang
Meng-Lei
ML
Huan
Bang-Le
BL
Zhang
Wei-Dong
WD
Zhang
Zeng-Hui
ZH
Teng
Hong-Quan
HQ
Gan
Si-Yuan
SY
Zhou
Yi
Y
Gu
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D031644:Ardisia / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D016014:Linear Models; D023421:Models, Animal; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D012503:Saponins; C087799:ardipusilloside I; D009828:Oleanolic Acid