Effects of naringenin on the pharmacokinetics of tofacitinib in rats. (1st January 2020)

• Record Type: Journal Article
• Authors: Wang, Bo; Shen, Jiquan; Zhou, Quan; Meng, Deru; He, Youwu; Chen, Feifei; Wang, Shuanghu; Ji, Weiping
• Is Part Of: Pharmaceutical biology. Volume 58:Number 1(2020)
• Page Start: 225
• Page End: 230
• Publication Date: 2020-01-01
• Subjects: Drug–drug interaction -- flavonoids -- CYP3A4; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2020.1738504
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context: Naringenin and tofacitinib are often used together for treatment of rheumatoid arthritis in Chinese clinics. Objective: This experiment investigates the effect of naringenin on the pharmacokinetics of tofacitinib in rats. Materials and methods: 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: Results indicated that naringenin could significantly affect the pharmacokinetics of tofacitinib. The AUC0–24 of tofacitinib was increased from 1222.81 ± 222.07 to 2016.27 ± 481.62 ng/mL/h, and the difference was significant ( p < 0.05). Compared with the control group, the T max was increased from 0.75 ± 0.29 to 3.00 ± 0.00 h ( p < 0.05), and the MRT(0–24) was increased from 4.90 ± 0.51 to 6.57 ± 0.66 h ( p < 0.05), but the clearance was obviously decreased from 4.10 ± 0.72 to 2.42 ± 0.70 L/h/kg ( p < 0.05) in experimental group. Although the C max and t 1/2 of tofacitinib were increased, there were no significant differences ( p > 0.05). Conclusions: 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.