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 lL 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 AUC 0-24 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.

Naringenin has an inhibitory effect on rivaroxaban in rats both in vitro and in vivo

“…Compared with the control group, pre-treatment of rats with naringenin for 2 weeks could increase the AUC, MRT, and T max values of tofacitinib by 1.76-fold, 1.60-fold, and 4.00-fold, respectively, but decreased its CL z/F by 1.69-fold. 20 Similarly, metabolisms of both ibrutinib and felodipine were inhibited, and their systemic exposures were also increased when co-administrated them with naringenin. It was supposed that naringenin might affect these two drugs by inhibiting the CYP3A4mediated metabolism.…”

Effects of Shaoyao-Gancao-Fuzi Decoction on the Pharmacokinetics of CYP3A4-Mediated Tofacitinib in Rats

“…The DDIs and HDIs are generally achieved by the pharmacokinetic properties, and may occur in the phase of absorption, distribution, metabolism or excretion. The CYP450 system is crucial for drug metabolism which is related to the metabolism of endogenous substances, detoxi cation of exogenous substances and activation of precarcinogens [13]. CYP450 superfamilies include CYP1, CYP2 and CYP3.…”

“…Nowadays, with the development of combine therapy of medicines, increasingly importance has been attached to drug-drug interactions (DDIs) and herbal-drug interactions (HDIs). Several studies on the DDIs and HDIs have been reported in the last few years [12][13][14]. Some ingredients could inhibit or induce the activities of drug-metabolizing enzymes or transporter proteins, which may change the absorption, distribution, metabolism and excretion of drugs, effecting its pharmacological activity and toxicity on concomitant administration.…”

Pharmacokinetic–pharmacodynamic modeling analysis and anti‐inflammatory effect of Wangbi capsule in the treatment of adjuvant‐induced arthritis

“…Finally, the PK-PD models were conducted successfully by combining PK and PD data collected after oral administration of WBC. (Zhang et al, 2016;Wang, Shen, et al, 2020).…”