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Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2.
Ren, Hong-Can; Sun, Jian-Guo; A, Ji-Ye; Gu, Sheng-Hua; Shi, Jian; Shao, Feng; Ai, Hua; Zhang, Jing-Wei; Peng, Ying; Yan, Bei; Huang, Qing; Liu, Lin-Sheng; Sai, Yang; Wang, Guang-Ji; Yang, Cheng-Guang.
Afiliación
  • Ren HC; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Sun JG; DMPK and Clinical Pharmacology Group, Hutchison MediPharma Ltd., Shanghai, China.
  • A JY; Department of Biology, GenFleet Therapeutics, Shanghai, China.
  • Gu SH; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Shi J; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Shao F; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Ai H; School of Pharmacy, Shanghai University of Tranditional Chinese Medicine, Shanghai, China.
  • Zhang JW; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Peng Y; College of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
  • Yan B; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Huang Q; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Liu LS; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Sai Y; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Wang GJ; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Yang CG; Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Front Pharmacol ; 13: 804377, 2022.
Article en En | MEDLINE | ID: mdl-35694247
Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form. Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation. Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2. Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza