Xin-yi-san contains potent human CYP1A2 inhibitors and its combined use with theophylline in treatment increases adverse risks in patients.
Phytomedicine
; 130: 155760, 2024 Jul 25.
Article
in En
| MEDLINE
| ID: mdl-38797029
ABSTRACT
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 Ki values of 77â84 nM, higher than those (20â52 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 2017â2018, 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), 1.99â2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21â2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07â1.72; 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, 0.14â0.40; 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Furocoumarins
/
Theophylline
/
Drugs, Chinese Herbal
/
Cytochrome P-450 CYP1A2
/
Angelica
/
Cytochrome P-450 CYP1A2 Inhibitors
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Phytomedicine
Journal subject:
TERAPIAS COMPLEMENTARES
Year:
2024
Type:
Article
Affiliation country:
Taiwan