Effects of naringenin on the pharmacokinetics of tofacitinib in rats

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). 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.

Keywords

• drug–drug interaction
• flavonoids
• cyp3a4