Abstract
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, respectively.
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.
Keywords: Zhenwu decoction, cytochrome P450, chronic heart failure, cocktail probe drug, enzyme activity, mRNA expression.
Graphical Abstract
Call for Papers in Thematic Issues
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Tissue Distribution and Metabolism of Micro- and Nanoparticles and Medical Implants
With the continuous advancement of modern science and engineering, numerous functional materials and active molecules have been developed and utilized in various industrial, medical, and food applications. Many of these can enter the body, either actively or passively, and have significant and intricate impacts on human health. For example, biomaterials ...read more
Related Books
Nanoparticles and Nanocarriers Based Pharmaceutical Formulations
Localized Micro/Nanocarriers for Programmed and On-Demand Controlled Drug Release
Advanced Pharmaceutical and Herbal Nanoscience for Targeted Drug Delivery Systems Part I
Advanced Pharmaceutical and Herbal Nanoscience for Targeted Drug Delivery Systems Part II
Mixed Polymeric Micelles for Osteosarcoma Therapy: Development and Characterization
A Comprehensive Text Book on Self-emulsifying Drug Delivery Systems
Nanomaterials: Evolution and Advancement towards Therapeutic Drug Delivery (Part II)
Nanomaterials: Evolution and Advancement Towards Therapeutic Drug Delivery (Part I)
45