Effect of decursin on the pharmacokinetics of theophylline and its metabolites in rats

Ethnopharmacological relevance: Decursin is used as a traditional Asian medicine to treat various women's diseases. Aim of the study: Herb-drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of decursin, on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. Materials and methods: After decursin pretreatment for 3 days, on the fourth day rats were administered decursin and theophylline concomitantly. The blood theophylline and its major metabolites (1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (1,3-DMU)) levels were monitored with LC-MS/MS. Results: The results indicated that the clearance, elimination rate constant (K-el) of theophylline was significantly decreased and area under concentration-time curve (AUC), C-max, half-life was increased in decursin (25 mg/kg) pretreatment when theophylline (10 mg/kg) was given. In the presence of decursin, the pharmacokinetic parameters of three metabolites (1-MX, 1,3-DMU, and 1-MU) were affected and the differences were statistically significant about AUC(24 h) parameter. Conclusion: 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) 2012 Published by Elsevier Ireland Ltd.