Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats
Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine “baishouwu”, which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, an...
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doaj-8fb0042366d14027986c08d46597ef262020-11-24T20:51:24ZengMDPI AGMolecules1420-30492015-03-012034225423710.3390/molecules20034225molecules20034225Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model RatsYunru Peng0Yongfang Ding1Department of Pharmacology and Toxicology, Jiangsu Provincial Institute of Traditional Chinese Medicine, 100 Shizi Street, Nanjing 210028, ChinaDepartment of Pharmacology and Toxicology, Jiangsu Provincial Institute of Traditional Chinese Medicine, 100 Shizi Street, Nanjing 210028, ChinaCaudatin is a potential antitumor agent isolated from the traditional Chinese medicine “baishouwu”, which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease.http://www.mdpi.com/1420-3049/20/3/4225pharmacokineticsC-21 steroidal glycosideCynanchum auriculatum Royle ex wightcaudatinhepatocellular carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yunru Peng Yongfang Ding |
spellingShingle |
Yunru Peng Yongfang Ding Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats Molecules pharmacokinetics C-21 steroidal glycoside Cynanchum auriculatum Royle ex wight caudatin hepatocellular carcinoma |
author_facet |
Yunru Peng Yongfang Ding |
author_sort |
Yunru Peng |
title |
Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats |
title_short |
Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats |
title_full |
Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats |
title_fullStr |
Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats |
title_full_unstemmed |
Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats |
title_sort |
pharmacokinetics and tissue distribution study of caudatin in normal and diethylnitrosamine-induced hepatocellular carcinoma model rats |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2015-03-01 |
description |
Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine “baishouwu”, which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease. |
topic |
pharmacokinetics C-21 steroidal glycoside Cynanchum auriculatum Royle ex wight caudatin hepatocellular carcinoma |
url |
http://www.mdpi.com/1420-3049/20/3/4225 |
work_keys_str_mv |
AT yunrupeng pharmacokineticsandtissuedistributionstudyofcaudatininnormalanddiethylnitrosamineinducedhepatocellularcarcinomamodelrats AT yongfangding pharmacokineticsandtissuedistributionstudyofcaudatininnormalanddiethylnitrosamineinducedhepatocellularcarcinomamodelrats |
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