Effects of Zuojin Pill (Rhizoma Coptidis and Fructus Evodiae preparation) on the pharmacokinetics and side effects of venlafaxine in humans
Dongmin Yan
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorMing Wu
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorWenjuan Hu
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Search for more papers by this authorYue Li
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorJingyi Jin
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorShaoqing Yan
Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorWei Zhu
Department of Clinical Pharmacy, Wuxi Yike Traditional Chinese Medicine Hospital, Wuxi, China
Search for more papers by this authorChaoyang Ye
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorJia Liu
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Search for more papers by this authorCorresponding Author
Guobin Liu
Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Correspondence
Bo Tan, Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Guobin Liu, Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Bo Tan
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Correspondence
Bo Tan, Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Guobin Liu, Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Search for more papers by this authorDongmin Yan
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorMing Wu
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorWenjuan Hu
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Search for more papers by this authorYue Li
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorJingyi Jin
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorShaoqing Yan
Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorWei Zhu
Department of Clinical Pharmacy, Wuxi Yike Traditional Chinese Medicine Hospital, Wuxi, China
Search for more papers by this authorChaoyang Ye
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Search for more papers by this authorJia Liu
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Search for more papers by this authorCorresponding Author
Guobin Liu
Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Correspondence
Bo Tan, Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Guobin Liu, Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Bo Tan
Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Correspondence
Bo Tan, Laboratory of Clinical Pharmacokinetics, Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Guobin Liu, Peripheral Vascular Disease Department, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Shanghai, China.
Email: [email protected]
Search for more papers by this authorDongmin Yan and Ming Wu contributed equally to the work.
Funding information: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Grant/Award Number: SGXZ-201907; Shanghai University of Traditional Chinese Medicine, Grant/Award Number: 2021LK075; Science and Technology Commission of Shanghai Municipality, Grant/Award Number: 21Y21920200; Shanghai Municipal Health Commission, Grant/Award Number: 201740199
Abstract
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 co-administration of ZJP was compared. ZJP had a weak herb–drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means of Cmax and AUC0-∞ 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.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest to disclose.
Supporting Information
| Filename | Description |
|---|---|
| bcpt13713-sup-0001-Supplementary data_20211112.docxWord 2007 document , 33.5 KB |
Table S1. Mass spectrometry parameters for measuring venlafaxine (VEN) and its two primary metabolites (O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV)), and four major alkaloids of Zuojin Pill (berberine, coptisine, evodiamine, and rutaecarpine) Table S2. The equations and measurement ranges for LC–MS/MS method Table S3. Intra- and inter-batch precision and accuracy of venlafaxine (VEN), O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV), berberine, coptisine, evodiamine, and rutaecarpine in human plasma (Mean ± SD, n = 5) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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