title: Effect of decursinol angelate on the pharmacokinetics of theophylline and its metabolites in rats.
abstract: Herb-drug interactions represent a serious problem as herbal medicine is used extensively in the modern 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.
authors: College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors: Jung-woo
authors: JW
authors: Chae
authors: Jung-hwa
authors: JH
authors: An
authors: Wonku
authors: W
authors: Kang
authors: Jin yeul
authors: Jy
authors: Ma
authors: Kwang-il
authors: KI
authors: Kwon
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001578:Benzopyrans / Q000378:metabolism / Q000493:pharmacokinetics*; D002087:Butyrates / Q000378:metabolism / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006207:Half-Life; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013806:Theophylline / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D013806:Theophylline; C101278:decursin