Interaction Effects between Doxorubicin and Hernandezine on the Pharmacokinetics by Liquid Chromatography Coupled with Mass Spectrometry

Doxorubicin (DOX) is an effective anti-tumor drug widely used in clinics. Hernandezine (HER), isolated from a Chinese medicinal herb, has a selective inhibitory effect on DOX multidrug resistance, making DOX more effective in treating cancer. The aim of this study was to investigate the effect of th...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-10, Vol.24 (19), p.3622
Main Authors: Song, Yang, Zhang, Yuan, Zhang, Wei-Peng, Zhang, Bao-Zhen, Wang, Ke-Fei, Feng, Xue-Song
Format: Article
Language:English
Subjects:
Accuracy
Benzylisoquinolines - pharmacokinetics
Calibration
Chromatography
Chromatography, Liquid
Doxorubicin
Doxorubicin - pharmacokinetics
Drug Interactions
Drugs, Chinese Herbal - pharmacokinetics
drug–drug interaction
HER protein
Herbal medicine
hernandezine
Investigations
Kinases
lc-ms/ms
Limit of Detection
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Molecular Structure
Multidrug resistance
Parameter estimation
pharmacokinetic study
Pharmacokinetics
Pharmacology
Plasma
Proteins
Ratios
Regression analysis
Retention
Tandem Mass Spectrometry
Tumors
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Summary:Doxorubicin (DOX) is an effective anti-tumor drug widely used in clinics. Hernandezine (HER), isolated from a Chinese medicinal herb, has a selective inhibitory effect on DOX multidrug resistance, making DOX more effective in treating cancer. The aim of this study was to investigate the effect of the interaction of HER and DOX on pharmacokinetics. Male Sparague-Dawley rats were randomly divided into three groups: a single DOX group, a single HER group, and a combination group. Plasma concentrations of DOX and HER were determined by the LC-MS/MS method at specified time points after administration, and the main pharmacokinetic parameters were estimated. The results showed that there were significant differences in the C and AUC of DOX in the single drug group and combined drug group, indicating that HER could improve the absorption of DOX. However, DOX in combination, in turn, reduced the free drug concentration of HER, possibly because DOX enhanced the HER drug-protein binding effect. The results could be used as clinical guidance for DOX and HER to avoid adverse reactions.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24193622