Effects of Mailuoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4 using a three-drug Cocktail approach

Abstract

Abstract: AIM: To investigate the effects of Mailuoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4.METHODS: 14 rats were randomly and equally divided into two groups, i.e.clinicallyequivalent-dose group and higher-dose group.Two group rats underwent 2-cycle pharmacokinetic experiments before and after being treated with two doses of Mailuoning injection for 14 days, in which the rats were concomitantly administered Theophylline (30mg/kg) , Chlorzoxazone (50 mg/kg) and Dapsone (20 mg/kg) by gastrogavage, followed by blood-withdrawing from orbital bleeding at different intervals within 24 hours.High-performance liquid chromatography (HPLC ) was utilized to simultaneously quantitate 3 probe compounds in rat plasma, and DAS 2.0 Software was used to fit plasma concentration-time curve and calculate their corresponding principal pharmacokinetic parameters, among which the statistical differences were evaluated by Pariedt-test.RESULTS: In the 14-day administration period, the 2-cycle pharmacokinetic parameters of 3 probes for the clinically-equivalent-dose group rats exhibited insignificant differences(P>0.05) , meanwhile, after being treated with higher-dose Mailuoning injection, there were no significant differences for theophylline pharmacokinetics in rats, but AUC0-24 h of dapsone and chlorzoxazone after treatment were 1.27 and 1.44 times larger than those before treatment, respectively and chlorzoxazone CLF became smaller.CONCLUSION: Clinically- equivalent- dose Mailuoning injection did not affect the activities of rat CYP1A2, CYP2E1 and CYP3A4 ;higher dose Mailuoning injection could not insignificantly change CYP1A2 activity, but could weakly inhibit activities of CYP2E1 and CYP3A4.

Key words: Mailuoning injection, cytochrome P450, Theophylline, Chlorzoxazone, Dapsone

CLC Number:

R969.1

CHEN Wei-kao, JU Wen-zheng, XU Li-jun, LIU Shi-jia, TAN Heng-shan. Effects of Mailuoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4 using a three-drug Cocktail approach[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(4): 386-390.

References

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