title: Absorption and metabolism characteristics of pristimerin as determined by a sensitive and reliable LC-MS/MS method.
abstract: In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of pristimerin in rat plasma, cell incubation media and metabolism incubation mixtures. The absolute oral bioavailability of pristimerin is 28.4% at a dose of 1 mg·kg(-1), and the bioavailability was poor. The bidirectional transport of pristimerin across Caco-2 cells was studied in vitro. A markedly higher transport of pristimerin across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the transport of pristimerin in intestine. The phase I and phase II metabolic stability was also investigated using human liver microsomes (HLM) and S9 fractions, respectively. Pristimerin was stable in S9 fractions but metabolized in HLM with a half-life of 20.4 min, which indicated that pristimerin could be mainly metabolized by phase I enzymes. In conclusion, the absolute oral bioavailability of pristimerin in plasma, transport across Caco-2 cell monolayers, and metabolic stability in HLM and S9 fractions were systematically investigated by using a sensitive and reliable LC-MS/MS method.
authors: Department of Pharmacy, Laiwu City People's Hospital, 001 Xuehu Street, North Changshao Road, Laicheng District, Laiwu City 271199, Shandong Province, China.
authors: Chuanhai
authors: C
authors: Dong
authors: Department of Pharmacy, Rizhao City People's Hospital, 126 Taian Road, Rizhao City 276800, Shandong Province, China.
authors: Chongde
authors: C
authors: Xu
authors: Department of Pharmacy, Laiwu City People's Hospital, 001 Xuehu Street, North Changshao Road, Laicheng District, Laiwu City 271199, Shandong Province, China; Department of Pharmacology, Taishan Medical University, 2 North Yingsheng Road, Taian City 271000, Shandong Province, China.
authors: Hui
authors: H
authors: Liu
authors: Department of Pharmacy, Laiwu City People's Hospital, 001 Xuehu Street, North Changshao Road, Laicheng District, Laiwu City 271199, Shandong Province, China.
authors: Shuna
authors: S
authors: Xu
authors: Department of Pharmacology, Taishan Medical University, 2 North Yingsheng Road, Taian City 271000, Shandong Province, China.
authors: Yunsheng
authors: Y
authors: Gao
authors: Department of Pharmacy, Laiwu City People's Hospital, 001 Xuehu Street, North Changshao Road, Laicheng District, Laiwu City 271199, Shandong Province, China. Electronic address: JianPeng_KY@163.com.
authors: Jian
authors: J
authors: Peng
mesh_terms: D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002853:Chromatography, Liquid; D006207:Half-Life; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D014315:Triterpenes / Q000493:pharmacokinetics*; D014700:Verapamil
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D014700:Verapamil; C050414:celastrol
keywords: Caco-2 cells; Glucose 6-phosphate (PubChem CID: 5958); Human liver microsomes; Hydrocortisone (PubChem CID: 5754); Lucifer yellow (PubChem CID: 93367); P-gp; Pharmacokinetics; Pristimerin; Pristimerin (PubChem CID: 159516); UDPGA (PubChem CID: 17473); Verapamil (PubChem CID: 62969); β-nicotinamide adenine dinucleotide phosphate (PubChem CID: 5884)