Department of Orthopaedics, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.
The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.
Pharm Biol. 2020 Dec;58(1):225-230. doi: 10.1080/13880209.2020.1738504.
Naringenin and tofacitinib are often used together for treatment of rheumatoid arthritis in Chinese clinics. This experiment investigates the effect of naringenin on the pharmacokinetics of tofacitinib in rats. Twelve Sprague-Dawley rats were randomly divided into two groups (experimental group and control group). The experimental group was pre-treated with naringenin (150 mg/kg/day) for two weeks before dosing tofacitinib, and equal amounts of CMC-Na solution in the control group. After a single oral administration of 5 mg/kg of tofacitinib, 50 μL blood samples were directly collected into 1.5 mL heparinized tubes via the caudal vein at 0.083, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. The plasma concentration of tofacitinib was quantified by UPLC/MS-MS. Results indicated that naringenin could significantly affect the pharmacokinetics of tofacitinib. The AUC of tofacitinib was increased from 1222.81 ± 222.07 to 2016.27 ± 481.62 ng/mL/h, and the difference was significant ( < 0.05). Compared with the control group, the was increased from 0.75 ± 0.29 to 3.00 ± 0.00 h ( < 0.05), and the MRT was increased from 4.90 ± 0.51 to 6.57 ± 0.66 h ( < 0.05), but the clearance was obviously decreased from 4.10 ± 0.72 to 2.42 ± 0.70 L/h/kg ( < 0.05) in experimental group. Although the and of tofacitinib were increased, there were no significant differences ( > 0.05). This research demonstrated a drug-drug interaction between naringenin and tofacitinib possibly when preadministered with naringenin; thus, we should pay attention to this possibility in the clinic.
柚皮素和托法替尼经常一起用于中国诊所治疗类风湿关节炎。本实验研究了柚皮素对大鼠体内托法替尼药代动力学的影响。将 12 只 Sprague-Dawley 大鼠随机分为两组（实验组和对照组）。实验组在给予托法替尼前两周用柚皮素（150mg/kg/天）预处理，对照组给予等体积的 CMC-Na 溶液。单剂量给予 5mg/kg 托法替尼后，通过尾静脉直接采集 50μL 血样至 1.5mL 肝素化管，时间点为 0.083、0.5、1、2、3、4、6、8、10、12 和 24h。采用 UPLC/MS-MS 定量测定托法替尼的血浆浓度。结果表明，柚皮素可显著影响托法替尼的药代动力学。托法替尼的 AUC 从 1222.81±222.07 增加到 2016.27±481.62ng/mL/h，差异有统计学意义（ <0.05）。与对照组相比，实验组的 从 0.75±0.29 增加到 3.00±0.00h（ <0.05），MRT 从 4.90±0.51 增加到 6.57±0.66h（ <0.05），但清除率从 4.10±0.72 明显降低到 2.42±0.70L/h/kg（ <0.05）。虽然托法替尼的 和 增加，但差异无统计学意义（ >0.05）。本研究表明，柚皮素与托法替尼预先给药时可能存在药物相互作用，因此，在临床中应注意这种可能性。
