Li Tonghui, Liu Jijun, Zheng Yingying, Yang Shengchang, Liu Xun, Li Xuejing
a Department of Pharmacy , the Third Hospital of Hebei Medical University , Shijiazhuang , China.
b Department of Pharmacy , the Second Hospital of Hebei Medical University , Shijiazhuang , China.
Xenobiotica. 2019 Feb;49(2):211-215. doi: 10.1080/00498254.2018.1438685. Epub 2018 Mar 6.
Triptolide and fenofibrate are often used together for the treatment of nephrotic syndrome in Chinese clinics. This study investigates the effects of triptolide on the pharmacokinetics of fenofibrate in rats and it potential mechanism. The pharmacokinetics of fenofibrate (20 mg/kg) with or without triptolide pretreatment (2 mg/kg/day for seven days) were investigated. Additionally, the inhibitory effects of triptolide on the metabolic stability of fenofibrate were investigated using rat liver microsome incubation systems. The results indicated that the C (35.34 ± 7.52 vs. 30.43 ± 6.45 μg/mL), t (6.17 ± 1.15 vs. 4.90 ± 0.82 h) and AUC (468.12 ± 35.84 vs. 416.35 ± 32.68 mg h L) of fenofibric acid decreased significantly (p < .05). The T of fenofibric acid increased significantly (p < .05) from 5.12 ± 0.36 to 6.07 ± 0.68 h. Additionally, the metabolic stability of fenofibrate was prolonged from 35.8 ± 6.2 to 48.6 ± 7.5 min (p < .05) with the pretreatment of triptolide. In conclusion, these results indicated that triptolide could affect the pharmacokinetics of fenofibric acid, possibly by inhibiting the metabolism of fenofibrate in rat liver when they were co-administered.
在中国临床中，雷公藤甲素和非诺贝特常联合用于治疗肾病综合征。本研究考察雷公藤甲素对大鼠体内非诺贝特药代动力学的影响及其潜在机制。研究了给予非诺贝特（20 mg/kg），同时或不给予雷公藤甲素预处理（2 mg/kg/天，共7天）后的药代动力学情况。此外，使用大鼠肝微粒体孵育系统考察了雷公藤甲素对非诺贝特代谢稳定性的抑制作用。结果表明，非诺贝特酸的C（35.34±7.52 vs. 30.43±6.45 μg/mL）、t（6.17±1.15 vs. 4.90±0.82 h）和AUC（468.12±35.84 vs. 416.35±32.68 mg h/L）显著降低（p<0.05）。非诺贝特酸的T从5.12±0.36显著增加至6.07±0.68 h（p<0.05）。此外，雷公藤甲素预处理后，非诺贝特的代谢稳定性从35.8±6.2延长至48.6±7.5 min（p<0.05）。总之，这些结果表明，雷公藤甲素与非诺贝特合用时，可能通过抑制大鼠肝脏中对非诺贝特的代谢，从而影响非诺贝特酸的药代动力学。
