Effect of Naoxintong Capsules on the Activities of CYP450 and Metabolism of Metoprolol Tartrate in Rats Evaluated by Probe Cocktail and Pharmacokinetic Methods

Ouyang, Hongwei; Shen, Jiayuan; Huang, Xuhua; Ma, Wenxue; Jia, Qi; Yao, Guangzhe; Tang, Zhidan; Zhang, Dandan; Sun, Mengjie; Azietaku, John Teye; Jia, Hao; Gao, Xiumei; Chang, Yan‐xu; He, Jun

doi:10.1155/2019/5242605

Cited by 8 publications

(4 citation statements)

References 38 publications

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“…In humans, the main CYP subtypes include CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, CYP2J2, and CYP3A4 ( Tang et al, 2017 ). These subtypes participate in the metabolism of more than 90% of prescription drugs and play an important role in clinical practice ( Ouyang et al, 2019 ). Inhibition or induction of CYP enzyme activity is the main cause of drug–drug or herb–drug interactions ( Chen et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Wang

Zhang

et al. 2022

Front. Pharmacol.

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The combination of Salvia miltiorrhiza (Danshen) and rivaroxaban is a promising treatment option in clinical practice in China, but the herb–drug interaction between Danshen and rivaroxaban remains unclear. Therefore, this study aims to reveal the interaction between Danshen and rivaroxaban. We not only investigated the inhibitory properties of Danshen tablet on rivaroxaban metabolism in rat and human liver microsomes but also evaluated the inhibitory effects of Danshen tablet and its eight active components (dihydrotanshinone I, tanshinone I, tanshinone IIA, cryptotanshinone, danshensu, salvianolic acid A, salvianolic acid B, and salvianolic acid C) on cytochrome P450 (CYP) enzymes. The results showed that Danshen tablet potently inhibited the metabolism of rivaroxaban in rat and human liver microsomes. In the CYP inhibition study, we found that dihydrotanshinone I, the active component of Danshen tablet, potently inhibited the activities of rat CYP3A and CYP2J, with IC50 values at 13.85 and 6.39 μM, respectively. In further inhibition kinetic study, we found that Danshen tablet is a mixed inhibitor in rivaroxaban metabolism in rat and human liver microsomes, with the Ki value at 0.72 and 0.25 mg/ml, respectively. In conclusion, there is a potential interaction between Danshen tablet and rivaroxaban. Danshen tablet inhibits the metabolism of rivaroxaban, which may be because its lipid-soluble components such as dihydrotanshinone I strongly inhibit the activities of CYP enzymes, especially CYP3A and CYP2J. Therefore, when Danshen tablet and rivaroxaban are used simultaneously in the clinic, it is necessary to strengthen the drug monitoring of rivaroxaban and adjust the dosage.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Wang

Zhang

et al. 2022

Front. Pharmacol.

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“…And the addition of NXT to clopidogrel exhibited increased antiplatelet effect in patients with CYP2C19∗2 gene mutation after percutaneous coronary intervention (PCI) ( Hui, 2011b ). Ouyang et al investigated the potential effects of NXT on the CYP450 activities in rats and evaluated the pharmacokinetics effect of NXT on metoprolol tartrate and found that NXT exerted significant effect on inducing CYP3A4 activity while inhibiting CYP2D6 activity in vivo , thus affecting the metabolism of metoprolol tartrate and its metabolites, suggesting the importance to have a widespread concern regarding the combined use of NXT and western medicine clinically especially those metabolized by CYP3A4 and CYP2D6, so as to prevent drug-drug-related toxicity and side effects ( Ouyang et al, 2019 ). The above pharmacokinetic studies laid a foundation for the research of NXT’s pharmacological mechanism and provide important information and scientific basis for further rational clinical application of NXT.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside

Zhang,

Chen,

Tang

et al. 2024

Front. Pharmacol.

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Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

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“…Chromatographic separation was achieved on a UPLC BEH-C 18 (2.1 × 50 mm, 1.7 µm) with 0.1% (v: v) formic acid in water (A) and acetonitrile (B) as the mobile phase with gradient elution. e total run time was only 3.8 min, which was more rapid than the methods that have been published [27][28][29][30]. e plasma samples were extracted by protein precipitation, which is simple, convenient, and time-saving compared with the liquid-liquid extraction methods reported in the literature [21,22].…”

Section: 1mentioning

confidence: 99%

Quantitation of Diclofenac, Tolbutamide, and Warfarin as Typical CYP2C9 Substrates in Rat Plasma by UPLC-MS/MS and Its Application to Evaluate Linderane-Mediated Herb-Drug Interactions

Zhang

Peng

Rao

et al. 2022

Journal of Analytical Methods in Chemistry

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Linderane (LDR), the main active and distinctive component of L. aggregate, is a mechanism-based inactivator of CYP2C9 in vitro, indicating the occurrence of herb-drug interactions. However, little is known about the changes of the pharmacokinetic properties of the common clinical drugs as CYP2C9 substrates after coadministration with LDR. In this study, a selective and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of diclofenac, tolbutamide, and warfarin as CYP2C9 substrates in rat plasma has been developed. Chlorzoxazone was employed as an internal standard (IS), and protein precipitation was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH-C18 (2.1 × 50 mm, 1.7 µm) with 0.1% (v:v) formic acid in water (A) and acetonitrile (B) as the mobile phase with gradient elution. The total run time was only 3.8 min. MS analysis was performed under multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The bioanalytical method was validated, and the selectivity, carryover effects, linearity, precision, accuracy, matrix effect, extraction recovery, and stability were acceptable. The validated method was then successfully applied for evaluating the potential pharmacokinetic interactions when LDR was used along with diclofenac, tolbutamide, and warfarin, respectively. Results showed that the Cmax of diclofenac in the treated group was 1287.82 ± 454.16 μg/L, which was about 5-fold of that in the control group P < 0.01 . The Cmax of tolbutamide in the treated group was 60.70 ± 10.70 mg/L, which was significantly decreased by about 25% when compared with the control group P < 0.01 . The Vd of warfarin in the treated group was obviously increased, which was about 1.4-fold of that in the control group P < 0.01 .

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Effect of Naoxintong Capsules on the Activities of CYP450 and Metabolism of Metoprolol Tartrate in Rats Evaluated by Probe Cocktail and Pharmacokinetic Methods

Cited by 8 publications

References 38 publications

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside

Quantitation of Diclofenac, Tolbutamide, and Warfarin as Typical CYP2C9 Substrates in Rat Plasma by UPLC-MS/MS and Its Application to Evaluate Linderane-Mediated Herb-Drug Interactions

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