The effect of apatinib on pharmacokinetic profile of buspirone both <i>in vivo</i> and <i>in vitro</i>

Zhang, Xiaodan; Li, Yinghui; Chen, Daoxing; You, Weiwei; Hu, Xiaoxia; Chen, Bingbing; Hu, Guoxin; Qian, Jianchang

doi:10.1111/jphp.13320

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Therefore, combining apatinib with fluvoxamine is an effective dosing strategy. Many studies had shown that apatinib interacts with antipsychotics like buspirone and venlafaxine (Bao et al, 2018;Zhang et al, 2020). In this study, the data demonstrated that it can also inhibit the metabolizing of fluvoxamine via suppression the activities of microsomes system, especially CYP2D6.…”

Section: Discussionmentioning

confidence: 62%

CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine

Chen²,

Gao³

et al. 2022

Front. Pharmacol.

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This study aimed 1) to investigate the influence of CYP2D6 variants on the catalyzing of fluvoxamine, and 2) to study the interaction between fluvoxamine and apatinib. An enzymatic reaction system was setup and the kinetic profile of CYP2D6 in metabolizing fluvoxamine was determined. In vivo, drug-drug interaction was investigated using Sprague–Dawley (SD) rats. Fluvoxamine was given gavage with or without apatinib. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentrations of fluvoxamine and desmethyl-fluvoxamine. The results demonstrated that the relative clearance rates of CYP2D6.A5V, V104A, D337G, F164L, V342M, R440C and R497C increased significantly compared with CYP2D6.1, ranging from 153.626% ± 6.718% to 394.310% ± 33.268%. The activities of other variants reduced to different extent, or even lost function, but there was no statistical difference. The IC50 of apatinib against fluvoxamine disposition was determined, which is 0.190 μM in RLM and 6.419 μM in HLM, respectively. In vivo, apatinib can enhance the plasma exposure of fluvoxamine remarkably characterized by increased AUC, Tmax and Cmax. Meanwhile, the produce of desmethyl fluvoxamine was dramatically inhibited, both AUC and Cmax decreased significantly. Mechanistically, apatinib inhibit the generation of fluvoxamine metabolite with a mixed manner both in RLM and HLM. Furthermore, there were differences in the potency of apatinib in suppressing fluvoxamine metabolism among CYP2D6.1, 2 and 10. In conclusion, CYP2D6 gene polymorphisms and drug-drug interaction can remarkably affect the plasma exposure of fluvoxamine. The present study provides basis data for guiding individual application of fluvoxamine.

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Section: Discussionmentioning

confidence: 62%

CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine

Chen²,

Gao³

et al. 2022

Front. Pharmacol.

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“…Previous laboratory experiments have shown that icotinib has an inhibitory effect on CYP3A ( Zhang et al, 2018 ). Moreover, it has been reported that apatinib inhibits the activity of cytochrome P450 enzymes ( Bao et al, 2018 ; Zhang et al, 2020 ). To further investigate this aspect, we conducted in vitro experiments using RLMs and HLMs.…”

Section: Discussionmentioning

confidence: 99%

The effect of icotinib or apatinib on the pharmacokinetic profile of oxycodone in rats and the underlying mechanism

Zhou,

Ye,

et al. 2023

PeerJ

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This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. In vivo, Sprague–Dawley (SD) male rats were administered oxycodone with or without icotinib or apatinib. Blood samples were collected and subjected to UPLC-MS/MS analysis. An enzyme incubation assay was performed to investigate the mechanism of drug–drug interaction using both rat and human liver microsomes (RLM and HLM). The results showed that icotinib markedly increased the AUC(0–t) and AUC(0–∞) of oxycodone but decreased the CLz/F. The Cmax of oxycodone increased significantly upon co-administration of apatinib. In vitro, the Km value of oxycodone metabolism was 101.7 ± 5.40 μM and 529.6 ± 19.60 μM in RLMs and HLMs, respectively. Icotinib and apatinib inhibited the disposition of oxycodone, with a mixed mechanism in RLM (IC50 = 3.29 ± 0.090 μM and 0.95 ± 0.88 μM, respectively) and a competitive and mixed mechanism in HLM (IC50 = 22.34 ± 0.81 μM and 0.48 ± 0.05 μM, respectively). In conclusion, both icotinib and apatinib inhibit the metabolism of oxycodone in vitro and in vivo. Therefore, the dose of oxycodone should be reconsidered when co-administered with icotinib or apatinib.

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“…However, there are also shortcomings in the biological treatment process. Skin inflammation, hypertension, gastrointestinal reactions, proteinuria, cytopenias, hand-foot syndrome, abdominal pain, and abdominal distension often occur during treatment, which can be alleviated by symptomatic supportive treatment [ 58 ]. It’s been reported that Apatinib is well tolerated and very effective in the treatment of advanced HCC, and it is beneficial in terms of objective remission rate and disease control rate [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of Apatinib combined with TACE in the treatment of hepatocellular carcinoma: a meta-analysis

Gong¹,

Li²

2022

World J Surg Onc

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Background The timely and effective treatments are vital to the prognosis of patients with hepatocellular carcinoma, and the role of Apatinib combined with TACE in the treatment of hepatocellular carcinoma remains unclear. Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of Apatinib combined with transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma. Methods We searched for randomized controlled trials (RCTs) on Apatinib and TACE use in the treatment of hepatocellular carcinoma. Cochrane Central Register of Controlled Trials, Embase, PubMed, China Biomedical Literature Database, China Knowledge Network, Wanfang Database, and Weipu Chinese Science and Technology Journal Database were searched up to 16 April 2021. Two researchers independently screened the literature and extracted data according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. This meta-analysis protocol had been registered online (available at: https://inplasy.com/inplasy-2021-6-0047/). Results A total of 14 RCTs involving 936 hepatocellular carcinoma patients were included. The objective remission rate (OR = 2.93, 95% CI 2.17–3.95), 1-year survival (OR = 2.47, 95% CI 1.65–3.68), 2-year survival (OR = 2.67, 95% CI 1.41–5.04), the incidence of hand-foot syndrome (OR = 32.09, 95% CI 10.87–94.74) and the incidence of proteinuria (OR = 14.79, 95% CI 6.07–36.06) of the Apatinib + TACE group was significantly higher than that of the TACE group (all P < 0.05). There were no significant differences in the incidence of myelosuppression (OR = 1.01, 95% CI 0.61–1.67), the incidence of hypertension (OR = 7.56, 95% CI 0.95–1.67, P = 60.17) between Apatinib + TACE and TACE group (all P > 0.05). Conclusions Apatinib combined with TACE is more effective than TACE alone in the treatment of hepatocellular carcinoma, but it has certain adverse reactions.

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The effect of apatinib on pharmacokinetic profile of buspirone both in vivo and in vitro

Cited by 4 publications

References 25 publications

CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine

CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine

The effect of icotinib or apatinib on the pharmacokinetic profile of oxycodone in rats and the underlying mechanism

The efficacy and safety of Apatinib combined with TACE in the treatment of hepatocellular carcinoma: a meta-analysis

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