Absorption and Metabolism Characteristics of Triptolide as Determined by a Sensitive and Reliable LC-MS/MS Method

Molecules

Xiaomei Gong²  Yan Chen¹  Yi Wu³ 

[1] Department of Gastroenterology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China; E-Mail:;Department of Radiatin Oncology, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai 200433, China;Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, 1# Weigang, Nanjing 210095, Jiangsu, China

关键词: Caco-2 cells;    human liver microsome;    P-gp;    pharmacokinetics;    triptolide;   

DOI  :  10.3390/molecules20058928

来源: mdpi

【 摘 要 】

In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of triptolide in rat plasma, microsomes, and cell incubation media. The absolute oral bioavailability of triptolide is 63.9% at a dose of 1 mg·kg⁻¹. In vitro, the bidirectional transport of triptolide across Caco-2 cells was studied. A markedly higher transport of triptolide 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 absorption of triptolide in intestinal. The metabolic stability was also investigated using human liver microsome incubation systems in vitro. In HLMs, incubations with an initial triptolide concentration of 1 μM resulted in an 82.4% loss of substrate over 60 min, and the t_1/2 was 38 min, which indicated that triptolide was easily metabolized in human liver microsomes. In conclusion, the absolute oral bioavailability of triptolide in plasma, transport across Caco-2 cell monolayers, and metabolic stability in human liver microsomes were systematically investigated by using a sensitive and reliable LC-MS/MS method.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.