title: Study on the pharmacokinetics profiles of polyphyllin I and its bioavailability enhancement through co-administration with P-glycoprotein inhibitors by LC-MS/MS method.
abstract: Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, is a promising natural anticancer candidate. Although the anticancer activity of PPI has been well demonstrated, information regarding the pharmacokinetics and bioavailability is limited. In this study, a series of reliable and rapid liquid chromatography-tandem mass spectrometry methods were developed and successfully applied to determinate PPI in rat plasma, cell incubation media and cell homogenate. Then the pharmacokinetics of PPI in rats was studied and the result revealed that PPI was slowly eliminated with low oral bioavailability (about 0.62%) at a dose of 50 mg/kg, and when co-administrated with verapamil (VPL) and cyclosporine A (CYA), the oral bioavailability of PPI could increase from 0.62% to 3.52% and 3.79% respectively. In addition, in vitro studies showed that with the presence of VPL and CYA in Caco-2 cells, the efflux ratio of PPI decreased from 12.5 to 2.96 and 2.22, and the intracellular concentrations increased 5.8- and 5.0-fold respectively. These results demonstrated that PPI, with poor oral bioavailability, is greatly impeded by P-gp efflux, and inhibition of P-gp can enhance its bioavailability.
authors.affiliation: Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Economic Administration Department, Weifang Engineering Vocational College, Weifang 262500, PR China.
authors.forename: Si-Can
authors.initials: SC
authors.lastname: Zhu
authors.affiliation: Kathmandu University, Kathmandu, Nepal.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Shakya
authors.affiliation: Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of pharmacy, Affiliated Hospital of Weifang Medical University, Weifang 261031, PR China.
authors.forename: Chuan-Hua
authors.initials: CH
authors.lastname: Ding
authors.affiliation: College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300222, PR China. Electronic address: longminhui2006@126.com.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Long
authors.affiliation: Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China. Electronic address: songlinli64@126.com.
authors.forename: Song-Lin
authors.initials: SL
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods; D016572:Cyclosporine / Q000008:administration & dosage; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000097:blood / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods; D014700:Verapamil / Q000008:administration & dosage
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D012503:Saponins; C556217:polyphyllin I; D016572:Cyclosporine; D014700:Verapamil; D004144:Diosgenin
keywords: Bioavailability; LC–MS/MS; P-glycoprotein; Pharmacokinetics; Polyphyllin I