Assessment of the effects of Radix bupleuri and vinegar-baked Radix bupleuri on cytochrome 450 activity by a six-drug cocktail approach.

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.