Background: Recently, the combination of Traditional Chinese Medicine (TCM) formulae and other
drugs has been used frequently in clinical practice, while the possibility of herb-drug interaction (HDI) risk remains a
challenge. Since metabolic enzymes mediate the majority of drug interactions, evaluating the effects of formulae on
metabolic enzymes is therefore instructive for the rational formulation of drug delivery plans.
Objective: Herein, we are devoted to estimating the effects of Zhenwu detection (ZWD) on activities and mRNA
expression of 7 cytochrome P450 (CYP450) isoenzymes in chronic heart failure (CHF) rats.
Methods: The CHF rats were replicated by coronary artery ligation and were randomly divided into sham operation
group, model group, ZWD low- (2.188 g/kg), middle- (4.375 g/kg), and high- (8.750 g/kg) dose groups, n=6. After 8
weeks, rats were administrated with ZWD and normal saline (NS) for four weeks, and the mixed solution of 7 probe
drugs (1 mL/kg) was subsequently injected into 30 rats through the caudal vein after the last administration. Pharmacokinetic
parameters and mRNA expression of 7 probe drugs were measured by using UPLC-MS/MS and RT-qPCR,
Results: Activities and mRNA expression of CYP1A2, CYP2B1, CYP2C6, CYP2C11, CYP3A1 were inhibited in
CHF rats, and ZWD could reverse this effect except for CYP2B1.
Conclusion: Overall, these findings underscore that for CHF patients, the HDI should be taken into consideration
when ZWD is used on its own or combined with drugs meditated by CYP1A2 (CYP1A2 in rats), CYP2C9 (CYP2C6
in rats), CYP2C19 (CYP2C11 in rats) and CYP3A4 (CYP3A1 in rats). Furthermore, since the apparent volume of
distribution (Vd) of amodiaquine, dextromethorphan and bupropion has been proved to be far greater than the total
volume of body fluids, we speculate that the dose adjustment and potential organotoxicity of these substrates may
need further consideration.