The effect of apatinib on pharmacokinetic profile of buspirone both in vivo and in vitro
| العنوان: | The effect of apatinib on pharmacokinetic profile of buspirone both in vivo and in vitro |
|---|---|
| المؤلفون: | Bingbing Chen, Wei-wei You, Ying-Hui Li, Xiao-dan Zhang, Xiao-xia Hu, Jian-chang Qian, Daoxing Chen, Guo-Xin Hu |
| المصدر: | Journal of Pharmacy and Pharmacology. 72:1405-1411 |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Pyridines, Cmax, Pharmaceutical Science, Pharmacology, 030226 pharmacology & pharmacy, High-performance liquid chromatography, Buspirone, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, In vivo, medicine, Animals, Drug Interactions, Apatinib, Protein Kinase Inhibitors, IC50, Dose-Response Relationship, Drug, Drug interaction, Rats, chemistry, 030220 oncology & carcinogenesis, Microsomes, Liver, medicine.drug |
| الوصف: | 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. |
| تدمد: | 2042-7158 0022-3573 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abc54adf2bd24c43dd400595bb9aaacaTest https://doi.org/10.1111/jphp.13320Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....abc54adf2bd24c43dd400595bb9aaaca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20427158 00223573 |
|---|