期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 184, 期 3, 页码 458-465出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2010.01.017
关键词
Herb-drug interaction; Andrographis paniculata; Andrographolide; Microdialysis; Pharmacokinetics
资金
- National Science Council, Taiwan [NSC96-2113-M-010-003-MY3, NSC96-2628-B-010-006-MY3]
- Taipei City Hospital, Taiwan [TCH 97002-62-037]
Herb-drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of Andrographis paniculata extract (APE) and its major component, andrographolide (AG), on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. After APE or AG pretreatment for 3 days, on the fourth day rats were administered theophylline via femoral vein cannula. The blood theophylline levels were monitored by microdialysis sampling combined with HPLC-UV. The results indicated that the clearance of theophylline was significantly increased and the area under concentration-time curve (AUC) was reduced in both AG and APE pretreated groups at low-dose theophylline administration (1 mg/kg). The elimination half-life (t(1/2 beta)) and mean residence time (MRT) of theophylline were shortened by 14% and 17%, respectively, in the AG pretreated group when high-dose theophylline (5 mg/kg) was given. However, theophylline accumulated in rat of the group with APE pretreatment. This phenomenon suggests that some other herbal components contained in APE may interact with theophylline and retard its elimination when theophylline was administered at a high dose. Our results suggest that patients who want to use CYP1A2-metabolized drugs such as caffeine and theophylline should be advised of the potential herb-drug interaction, to reduce therapeutic failure or increased toxicity of conventional drug therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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