دورية أكاديمية
أعرض في EDS

Xin-yi-san contains potent human CYP1A2 inhibitors and its combined use with theophylline in treatment increases adverse risks in patients.

التفاصيل البيبلوغرافية
العنوان: Xin-yi-san contains potent human CYP1A2 inhibitors and its combined use with theophylline in treatment increases adverse risks in patients.
المؤلفون: Kao LT; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan., Chen AC; Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan; Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan., Wang HJ; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan., Wen YL; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan., Lu CK; Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Liaw CC; Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Tsai KC; Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Ueng YF; Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan; Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ueng@nricm.edu.tw.
المصدر: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jul 25; Vol. 130, pp. 155760. Date of Electronic Publication: 2024 May 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE
أسماء مطبوعة: Publication: Stuttgart : Urban & Fischer Verlag
Original Publication: Stuttgart ; New York : G. Fischer, c1994-
مواضيع طبية MeSH: Theophylline*/pharmacology , Drugs, Chinese Herbal*/pharmacology , Cytochrome P-450 CYP1A2*/metabolism , Cytochrome P-450 CYP1A2 Inhibitors*/pharmacology , Angelica*/chemistry , Furocoumarins*/pharmacology, Humans ; Male ; Herb-Drug Interactions ; Retrospective Studies ; Female ; Taiwan ; Middle Aged ; Adult ; Oxidation-Reduction ; Rhinitis, Allergic/drug therapy ; Rhinitis, Allergic/chemically induced
مستخلص: Background: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index.
Purpose: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients.
Methods: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed.
Results: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with K i values of 77‒84 nM, higher than those (20‒52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017‒2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99‒2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21‒2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07‒1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14‒0.40; p < 0.001).
Conclusion: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
فهرسة مساهمة: Keywords: Adverse effect; Cytochrome P450; Imperatorin; Theophylline; Xin-yi-san
المشرفين على المادة: C137DTR5RG (Theophylline)
0 (Drugs, Chinese Herbal)
EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
0 (Cytochrome P-450 CYP1A2 Inhibitors)
0 (Furocoumarins)
EC 1.14.14.1 (CYP1A2 protein, human)
K713N25C78 (imperatorin)
تواريخ الأحداث: Date Created: 20240526 Date Completed: 20240614 Latest Revision: 20240716
رمز التحديث: 20240716
DOI: 10.1016/j.phymed.2024.155760
PMID: 38797029
قاعدة البيانات: MEDLINE
الوصف
تدمد:1618-095X
DOI:10.1016/j.phymed.2024.155760