The Effect of Apatinib on the Metabolism of Carvedilol Both in vitro and in vivo

Abstract

Background: In light of the growing number of cancer survivors, the incidence of cardiovascular complications in these patients had also increased, while the effect of apatinib on the pharmacokinetic of cardioprotective drug (carvedilol) in rats or human is still unknown. The present work was to study the impact of apatinib on the metabolism of carvedilol both in vitro and vivo. Methods: A specific and sensitive ultra-performance liquid-chromatography tandem mass spectrometry method was applied to determine the concentration of carvedilol and its metabolites (4′-hydroxyphenyl carvedilol [4′-HPC], 5′-hydroxyphenyl carvedilol [5′-HPC] and o-desmethyl carvedilol [o-DMC]). Results: The inhibition ratios in human liver microsomes were 10.28, 10.89 and 5.94% for 4′-HPC, 5′-HPC and o-DMC, respectively, while in rat liver microsomes, they were 3.22, 1.58 and 1.81%, respectively. The data in vitro of rat microsomes were consistent with the data in vivo that the inhibition of 4′-HPC and 5′-HPC formation was higher than the control group. Conclusion: Our study showed that apatinib could significantly inhibit the formation of carvedilol metabolites both in human and rat liver microsomes. It is recommended that the effect of apatinib on the metabolism of carvedilol should be noted and carvedilol plasma concentration should be monitored.

The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study

“…15 In contrast, antiangiogenic agents that inhibit VEGFR-2 and block VEGF-stimulated endothelial cell migration and proliferation have been shown to decrease tumor microvascular density and promote apoptosis. 16 Therefore, TACE in combination with targeted antiangiogenic drugs might be able to suppress the growth of both the tumor body as well as blood vessel simultaneously. Indeed, Wu et al showed that TACE together with sorafenib significantly prolonged the 5-year OS in TACE-refractory advanced HCC compared with the TACE group.…”

Evaluation of the Effects of Apatinib on the Pharmacokinetics of Venlafaxine and O‐desmethylvenlafaxine in SD Male Rats by UPLC–MS/MS

“…In view of the potential of Apa in the field of anticancer drugs and the widespread use of Ven in the field of antidepressant drugs, it makes sense to study whether there is an interaction between the two drugs. To our knowledge, there are no studies regarding these two drugs in combination, but there are some similar methods about interactions of Ven and Apa with other compounds, like the effect of apigenin on Ven and the effect of Apa on carvedilol . In this study, we examined the pharmacokinetics of Ven in rats after administration of Apa and identified the effect as well as the mechanisms of Apa on Ven in human and rat liver microsome.…”