Assessment of the effects of Radix bupleuri and vinegar-baked Radix bupleuri on cytochrome 450 activity by a six-drug cocktail approach.
10.1016/S1875-5364(13)60033-3
- Author:
Ying CHENG
1
;
Yin HUANG
;
Yuan TIAN
;
Lei XU
;
Guo-Qiang LIU
;
Zun-Jian ZAHNG
Author Information
1. Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bupleurum;
chemistry;
Chemistry, Pharmaceutical;
Cytochrome P-450 Enzyme Inhibitors;
Cytochrome P-450 Enzyme System;
chemistry;
metabolism;
Drugs, Chinese Herbal;
chemistry;
pharmacokinetics;
Enzyme Inhibitors;
chemistry;
pharmacokinetics;
Kinetics;
Male;
Mass Spectrometry;
Rats;
Rats, Sprague-Dawley
- From:
Chinese Journal of Natural Medicines (English Ed.)
2013;11(3):302-308
- CountryChina
- Language:English
-
Abstract:
AIM:To assess the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity of rats.
METHODS:Six probe drugs (caffeine, midazolam, dextromethorphan, tolbutamide, omeprazole, chlorzoxazone) were simultaneously given to rats after different dosing of Radix Bupleuri or vinegar-baked Radix Bupleuri for seven days. The plasma concentrations of the six probes were measured by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS) and their corresponding pharmacokinetic parameters were calculated.
RESULTS:The AUC and T1/2 of midazolam, dextromethorphan and chlorzoxazone decreased significantly (P < 0.05) in rats after different dosing of Radix Bupleuri or vinegar-baked Radix Bupleuri for seven days. Treatment of Radix Bupleuri decreased T1/2 and AUC of omeprazole, but treatment of vinegar-baked Radix Bupleuri with normal dose did not change the pharmacokinetics of omeprazole. The pharmacokinetics of tolbutamide in all vinegar-baked Radix Bupleuri-treated rats showed no statistically significant difference (P > 0.05) from that of controlled rats, however, treatment of Radix Bupleuri decreased tolbutamide T1/2. The pharmacokinetics of caffeine in all Radix Bupleuri or vinegar-baked Radix Bupleuri-treated rats showed no statistically significant difference (P > 0.05) from that of controlled rats.
CONCLUSION:The Radix Bupleuri and vinegar-baked Radix Bupleuri have different effects on the CYP2C9 and CYP2C19. Radix Bupleuri and vinegar-baked Radix Bupleuri have strong induction effects on the CYP2E1, CYP2D6 and CYP3A4, however, have no impact on CYP1A2. The reason of different therapeutic effects of Radix Bupleuri and vinegar-baked Radix Bupleuri extract may be the different effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on the CYP2C9 and CYP2C19.
