The effect of apatinib on pharmacokinetic profile of buspirone both in vivo and in vitro
- J Pharm Pharmacol. 2020 Oct;72(10):1405-1411. doi: 10.1111/jphp.13320.
- 1. The Seventh People's Hospital of Wenzhou, Wenzhou, Zhejiang, China.
- 2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
- 3. Jinhua Hospital of Zhejiang University and Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.
Objective: In this study, we aimed to investigate the potential interaction of apatinib and buspirone and underlying mechanism.
Methods: UPLC-MS/MS assay was applied to determine the concentrations of buspirone and its main metabolites (1-PP and 6-OH buspirone) after incubated with liver microsomes. Moreover, the connection of in vitro and in vivo was further determined. Sprague Dawley rats were randomly divided into two groups: group A (20 mg/kg buspirone) and group B (buspirone vs 40 mg/kg apatinib). Tail vein blood was collected and subjected to the UPLC-MS/MS detection.
Key findings: Apatinib inhibited the generations of 1-PP and 6-OH buspirone dose-dependently with IC50 of 1.76 and 2.23 μm in RLMs, and 1.51 and 1.48 μm in HLMs, respectively. There was a mixed mechanism underlying such an inhibition effect. In rat, AUC(0- t ) , AUC(0-∞) , Tmax and Cmax of buspirone and 6-OH buspirone increased significantly while co-administering with apatinib, but Vz/F and CLz/F decreased obviously while comparing group A with group B .
Conclusions: Apatinib suppresses the CYP450 based metabolism of buspirone in a mixed mechanism and boosted the blood exposure of prototype drug and 6-OH buspirone dramatically. Therefore, extra caution should be taken when combining apatinib with buspirone in clinic.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Endogenous MetaboliteResearch Areas: Neurological Disease
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Research Areas: Neurological Disease