Ueng Yune-Fang, Tsai Tung-Hu, Don Ming-Jaw, Chen Ruei-Ming, Chen Ta-Liang
National Research Institute of Chinese Medicine, Taipei, Taiwan, R.O.C.
J Pharm Pharmacol. 2005 Feb;57(2):227-32. doi: 10.1211/0022357055489.
Rutaecarpine is a main active alkaloid present in the medicinal herb, Evodia rutaecarpa. The cytochrome P450 (CYP) 1A2 substrate, theophylline, is an important therapeutic agent for the treatment of asthma, but has a narrow therapeutic index. To evaluate the pharmacokinetic interaction of theophylline with rutaecarpine, the effects of rutaecarpine on CYP1A2 activity and theophylline pharmacokinetics were investigated. Oral treatment of Sprague-Dawley rats with 50 mg kg(-1) rutaecarpine for three days through a gastrogavage caused a 4- and 3-fold increase in liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activity, respectively. In the kidney, rutaecarpine treatment caused a 3-fold increase in EROD activity. In the lungs, EROD activity was elevated from an undetectable to a detectable level by rutaecarpine. Pharmacokinetic parameters of theophylline were determined using a microdialysis sampling method. Rutaecarpine pre-treatment increased the clearance of theophylline in a dose-dependent manner. Pre-treatment of rats with 50 mg kg(-1) rutaecarpine caused a 3-fold increase in theophylline clearance and a 70%, 68% and 68% decrease in the area under the concentration-time curve (AUC), mean residence time (MRT) and half-life, respectively. These results demonstrated that rutaecarpine treatment elevated CYP1A2 catalytic activity and theophylline excretion in rats. In patients taking theophylline, adverse effects might be noticed when a rutaecarpine-containing herbal preparation is used concomitantly.
吴茱萸碱是药用植物吴茱萸中的一种主要活性生物碱。细胞色素P450（CYP）1A2底物茶碱是治疗哮喘的重要治疗药物，但其治疗指数较窄。为了评估茶碱与吴茱萸碱的药代动力学相互作用，研究了吴茱萸碱对CYP1A2活性和茶碱药代动力学的影响。通过胃管给Sprague-Dawley大鼠口服50 mg kg⁻¹吴茱萸碱，连续三天，导致肝微粒体7-乙氧基异吩恶唑酮O-脱乙基酶（EROD）和7-甲氧基异吩恶唑酮O-脱甲基酶活性分别增加4倍和3倍。在肾脏中，吴茱萸碱处理使EROD活性增加3倍。在肺中，吴茱萸碱使EROD活性从不可检测水平提高到可检测水平。采用微透析采样法测定茶碱的药代动力学参数。吴茱萸碱预处理以剂量依赖的方式增加了茶碱的清除率。用50 mg kg⁻¹吴茱萸碱预处理大鼠，使茶碱清除率增加3倍，浓度-时间曲线下面积（AUC）、平均驻留时间（MRT）和半衰期分别降低70%、68%和68%。这些结果表明，吴茱萸碱处理提高了大鼠CYP1A2的催化活性和茶碱排泄。在服用茶碱的患者中，同时使用含吴茱萸碱的草药制剂可能会出现不良反应。
