1. Absorption and metabolism characteristics of pristimerin as determined by a sensitive and reliable LC–MS/MS method.
- Author
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Dong, Chuanhai, Xu, Chongde, Liu, Hui, Xu, Shuna, Gao, Yunsheng, and Peng, Jian
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ALTERNATIVE medicine , *ANIMAL experimentation , *BIOAVAILABILITY , *BIOLOGICAL models , *BIOLOGICAL transport , *BIOPHYSICS , *ENZYMES , *LIQUID chromatography , *LIVER , *MASS spectrometry , *RESEARCH methodology , *MEDICINAL plants , *ORAL drug administration , *RATS , *PLANT extracts , *DESCRIPTIVE statistics , *IN vitro studies ,RESEARCH evaluation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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