Lack of pharmacokinetic interaction between derazantinib and naringin in rats

Context: Derazantinib-an orally bioavailable, ATP competitive, multikinase inhibitor-has strong activity against fibroblast growth factor receptors (FGFR)2, FGFR1, and FGFR3 kinases. It has preliminary antitumor activity in patients with unresectable or metastatic FGFR2 fusion-positive intrahepatic cholangiocarcinoma (iCCA).

Objective: This experiment validates a novel sensitive and rapid method for the determination of derazantinib concentration in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), and applies it to the study of drug-drug interaction between derazantinib and naringin in vivo.

Materials and methods: A Xevo TQ-S triple quadrupole tandem mass spectrometer was used for mass spectrometry monitoring in selective reaction monitoring (SRM) mode with transitions of m/z 468 96 → 382.00 for derazantinib and m/z 488.01 → 400.98 for pemigatinib, respectively. The pharmacokinetics of derazantinib (30 mg/kg) was investigated in Sprague-Dawley (SD) rats divided into two groups (with the oral pretreatment of 50 mg/kg naringin or not).

Results: The newly optimized UPLC-MS/MS method was suitable for the determination of derazantinib in rat plasma. It was also successfully employed to evaluate the effect of naringin on derazantinib metabolism in rats. After pretreatment with naringin, there was no significant difference in the pharmacokinetic parameters (AUC0→t, AUC0→∞, t1/2, CLz/F, and Cmax) of derazantinib when compared with derazantinib alone.

Conclusion: Co-administration of naringin with derazantinib was not associated with significant changes in pharmacokinetic parameters. Thus, this study suggests that the combination of derazantinib with naringin can safely be administered concomitantly without dose adjustment.

 

Comments:

Based on the provided context, here is a summary of the experiment and its findings:

**Objective:** The objective of this experiment was to validate a sensitive and rapid method for measuring derazantinib concentration in rat plasma using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The method was then applied to study the interaction between derazantinib and naringin in vivo.

**Materials and Methods:** The researchers used a specific mass spectrometer and selective reaction monitoring mode for monitoring derazantinib. The pharmacokinetics of derazantinib were studied in rats, which were divided into two groups: one group received oral pretreatment of naringin, while the other did not.

**Results:** The optimized UPLC-MS/MS method was successful in determining derazantinib concentration in rat plasma. The study also investigated the impact of naringin on derazantinib metabolism. Surprisingly, after pretreatment with naringin, there were no significant differences in key pharmacokinetic parameters (AUC0→t, AUC0→∞, t1/2, CLz/F, and Cmax) of derazantinib when compared with derazantinib administered alone.

**Conclusion:** The co-administration of naringin with derazantinib did not cause significant changes in derazantinib's pharmacokinetic parameters. Therefore, the study suggests that derazantinib and naringin can be safely administered together without requiring a dose adjustment.

In summary, the experiment successfully developed a method for monitoring derazantinib concentration and demonstrated that when combined with naringin, derazantinib's effectiveness and metabolism remain stable, indicating a safe combination for concurrent administration.

Related Products

Cat.No.	Product Name	Information
S8609	Derazantinib	Derazantinib is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with IC50 values of 1.8 nM for FGFR2, and 4.5 nM for FGFR1 and 3, showing lower potency for FGFR4 (IC50=34 nM). It also inhibits RET, DDR2, PDGFRβ, VEGFR and KIT.

Related Targets

FGFR