Effect of decursinol angelate on the pharmacokinetics of theophylline and its metabolites in rats

Title
Effect of decursinol angelate on the pharmacokinetics of theophylline and its metabolites in rats
Author(s)
강원구채정우[채정우]안정화[안정화]마진열[마진열]권광일[권광일]
Keywords
HERB-DRUG INTERACTION; ANGELICA-GIGAS; MASS-SPECTROMETRY; LIVER-MICROSOMES; PROSTATE-CANCER; COUMARINS; ROOT; ERYTHROLEUKEMIA; INVOLVEMENT; EXTRACT
Issue Date
201210
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.50, no.10, pp.3666 - 3672
Abstract
Herb-drug interactions represent a serious problem as herbal medicine is used extensively in the modem world. This study investigated the effects of decursinol angelate on the pharmacokinetics of theophylline, a typical substrate of the cytochrome P450 1A2 enzyme, in rats. After 3 days of decursinol angelate pretreatment, on the fourth day, rats were administered decursinol angelate and theophylline concomitantly. Blood theophylline and its major metabolite [1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (1,3-DMU)] levels were monitored by liquid chromatography-tandem mass spectroscopy. The results indicated that theophylline clearance significantly decreased and the area under the concentration-time curve (AUC) increased in decursinol angelate (25 mg/kg)-pretreated rats administered theophylline (10 mg/kg). The elimination half-life (t1/2) of theophylline was increased by 20%. In the presence of decursinol angelate (25 mg/kg), the pharmacokinetic parameters of three metabolites (1-MX, 1,3-DMU, and 1-MU) were significantly altered (half-life for 1-MU, and AUC24 h for 1-MX, 1,3-DMU, and 1-MU). Our results suggest that patients receiving CYP1A2-metabolized drugs, such as caffeine and theophylline, should be advised of the potential herb-drug interaction to reduce the risk of therapeutic failure or increased toxicity of conventional drug therapy. (c) 2012 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/27129http://dx.doi.org/10.1016/j.fct.2012.06.049
ISSN
0278-6915
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약학대학 > 약학부 > Articles
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