Effects of the Chinese herbal formula “Zuojin Pill” on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype

Qiu, Furong; Liu, Songcan; Miao, Ping; Jin, Zhao-Hui; Zhu, Leilei; Ye, Yujie; Jiang, Jian

doi:10.1007/s00228-016-2048-7

Cited by 14 publications

(20 citation statements)

References 21 publications

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“…Several traditional Chinese herbal medicines have been shown to increase or decrease drug metabolism by inducing or inhibiting CYP enzymes in preclinical models and/or clinical drug–drug interaction studies. As examples, ephedra, which is used for the treatment of patients with asthma, induces CYP1A2, whereas the herbal formula known as the “Zuojin Pill,” traditionally used to treat gastritis and gastric ulcers, inhibits CYP2D6 …”

Section: Clinical Pharmacology Assessment Of Ethnic Sensitivity Of Onmentioning

confidence: 99%

Challenges and Opportunities With Oncology Drug Development in China

Bajaj

Gupta

Wang³

et al. 2018

Clin Pharma and Therapeutics

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Section: Clinical Pharmacology Assessment Of Ethnic Sensitivity Of Onmentioning

confidence: 99%

Challenges and Opportunities With Oncology Drug Development in China

Bajaj

Gupta

Wang³

et al. 2018

Clin Pharma and Therapeutics

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“…However, administration of ZJW inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibition of CYP2D6 by ZJW could result in clinically relevant effects, either beneficial or deleterious, depending on the nature of the CYP2D6 genotype [48]. These findings would be helpful for a better understanding of the activities and clinical applications of ZJW.…”

Section: Discussionmentioning

confidence: 99%

Zuo Jin Wan Reverses DDP Resistance in Gastric Cancer through ROCK/PTEN/PI3K Signaling Pathway

Sun

Tao

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Gastric cancer (GC) is the third leading cause of cancer-related death. Chemotherapy resistance remains the major reason for GC treatment failure and poor overall survival of patients. Our previous studies have proved that Zuo Jin Wan (ZJW), a traditional Chinese medicine (TCM) formula, could significantly enhance the sensitivity of cisplatin (DDP)-resistant gastric cancer cells to DDP by inducing apoptosis via mitochondrial translocation of cofilin-1. However, the underlying mechanism remains poorly understood. This study aimed to evaluate the effects of ROCK/PTEN/PI3K on ZJW-induced apoptosis in vitro and in vivo. We found that ZJW could significantly activate the ROCK/PTEN pathway, inhibit PI3K/Akt, and promote the apoptosis of SGC-7901/DDP cells. Inhibition of ROCK obviously attenuated ZJW-induced apoptosis as well as cofilin-1 mitochondrial translocation, while inhibition of PI3K had the opposite effects. In vivo, combination treatment of DDP and ZJW (2000 mg/kg) significantly reduced tumor growth compared with DDP alone. Moreover, the combined administration of ZJW and DDP increased the expression of cleaved ROCK and p-PTEN while it decreased p-PI3K and p-cofilin-1, which was consistent with our in vitro results. These findings indicated that ZJW could effectively inhibit DDP resistance in GC by regulating ROCK/PTEN/PI3K signaling and provide a promising treatment strategy for gastric cancer.

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“…On the basis of moderate pharmacokinetic interactions between ZJP and dextromethorphan, a specific CYP2D6 probe substrate, a HDI study between ZJP and VEN in humans would be valuable for clinical treatment. 19 Therefore, the study was designed to determine whether there was a significant pharmacokinetic interaction between ZJP and VEN in healthy participants, and to explore whether the incidence of VEN-related side effects would be affected by concomitant use.…”

Section: Introductionmentioning

confidence: 99%

“…To date, however, no clinical study has been conducted to determine the clinical relevance of this interaction. On the basis of moderate pharmacokinetic interactions between ZJP and dextromethorphan, a specific CYP2D6 probe substrate, a HDI study between ZJP and VEN in humans would be valuable for clinical treatment 19 …”

Section: Introductionmentioning

confidence: 99%

Effects of Zuojin Pill (Rhizoma CoptidisandFructus Evodiaepreparation) on the pharmacokinetics and side effects of venlafaxine in humans

Yan

et al. 2022

Basic Clin Pharma Tox

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Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae, are high likely co-administered in China. ZJP could significantly inhibit VEN pharmacokinetics in vitro and in rats through suppression of CYP2D6 activity.To date, however, no clinical study has demonstrated the clinical relevance.Here, the VEN pharmacokinetics at a single dose of VEN with or without coadministration of ZJP was compared. ZJP had a weak herb-drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means of C max and AUC 0-∞ of VEN increased by 36.7% and 34.6%, respectively, and the corresponding 90% confidence intervals (CIs) of geometric mean ratios (GMRs) exceed outside bioequivalent range of 0.80-1.25. However, the corresponding 90% CIs of GMRs of these parameters for ODV were within the range. Since ODV exposure (AUC), approximately 3.4-fold higher than that of VEN, hardly changed, the systemic exposure of VEN active moiety (VEN + ODV) with ZJP increased slightly (≤8.5%) compared with that of VEN alone. In addition, the incidence of VEN-related side effects, especially gastrointestinal relevance, was significantly reduced with ZJP. Therefore, rational concomitant use of VEN and ZJP might have low risk of HDI and be promising in clinical practice. Dongmin Yan and Ming Wu contributed equally to the work.

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Effects of the Chinese herbal formula “Zuojin Pill” on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype

Abstract: These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D61/1 and CYP2D61/10 groups than CYP2D6 10/10 group.

Cited by 14 publications

References 21 publications

Challenges and Opportunities With Oncology Drug Development in China

Challenges and Opportunities With Oncology Drug Development in China

Zuo Jin Wan Reverses DDP Resistance in Gastric Cancer through ROCK/PTEN/PI3K Signaling Pathway

Effects of Zuojin Pill (Rhizoma CoptidisandFructus Evodiaepreparation) on the pharmacokinetics and side effects of venlafaxine in humans

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Effects of the Chinese herbal formula “Zuojin Pill” on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype

Abstract: These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10 groups than CYP2D6 *10/*10 group.

Cited by 14 publications

References 21 publications

Challenges and Opportunities With Oncology Drug Development in China

Challenges and Opportunities With Oncology Drug Development in China

Zuo Jin Wan Reverses DDP Resistance in Gastric Cancer through ROCK/PTEN/PI3K Signaling Pathway

Effects of Zuojin Pill (Rhizoma CoptidisandFructus Evodiaepreparation) on the pharmacokinetics and side effects of venlafaxine in humans

Contact Info

Product

Resources

About

Abstract: These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D61/1 and CYP2D61/10 groups than CYP2D6 10/10 group.