Inhibitory Effect of Apigenin on Pharmacokinetics of Venlafaxine in vivo and in vitro

Zhan, Yun-Yun; Liang, Bo; Gu, Er-min; Hu, Xiaoxia; Lin, Dan; Hu, Guoxin; Zheng, Zhiqiang

doi:10.1159/000437056

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…Furthermore, the presence of apigenin may be a contributing factor to improve the systemic exposure of other CYP2C9 substrates such as (S)-warfarin, tolbutamide, phenytoin, and acenocoumarol in vivo [19] . And our previous studies indicated that the coadministration in rat with apigenin could increase the absorption of imatinib and venlafaxine [29,30] . Meanwhile, further interaction investigations between apigenin and clinical drugs in vivo studies should be carried out.…”

Section: Discussionmentioning

confidence: 95%

Inhibitory Effect of Apigenin on Losartan Metabolism and CYP2C9 Activity in vitro

Wang

Gong²,

Zeng³

et al. 2016

Pharmacology

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Background: CYP2C9 is one of the most important phase I drug-metabolizing enzymes in liver. The objective of this work was to investigate the effects of apigenin on the metabolism of losartan and human CYP2C9 and rat CYP2C11 activity in vitro. Methods: Different concentrations of apigenin were added to a 100 mmol/l Tris-HCl reaction mixture containing 2 pmol/ml recombinant human CYP2C9.1, 0.25 mg/ml human liver microsomes or 0.5 mg/ml rat liver microsomes to determine the half maximal inhibition or a half-maximal inhibitory concentration (IC50) on the metabolism of losartan. In addition, diclofenac used as CYP2C9 substrate was performed to determine the effects of apigenin on CYP2C9. Results: The results showed that apigenin has the inhibitory effect on the metabolism of losartan in vitro, the IC50 was 7.61, 4.10 and 11.07 μmol/l on recombinant CYP2C9 microsomes, human liver microsomes and rat liver microsomes, respectively. Meanwhile, apigenin's mode of action on human CYP2C9 activity was competitive for the substrate diclofenac. In contrast to its potent inhibition of CYP2C9 in humans (9.51 μmol/l), apigenin had lesser effects on CYP2C11 in rat (IC50 = 15.51 μmol/l). Conclusion: The observations imply that apigenin has the inhibitory effect on the metabolism of losartan and CYP2C9 activity in vitro. More attention should be paid as to when losartan should be administrated combined with apigenin.

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Section: Discussionmentioning

confidence: 95%

Inhibitory Effect of Apigenin on Losartan Metabolism and CYP2C9 Activity in vitro

Wang

Gong²,

Zeng³

et al. 2016

Pharmacology

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“…The experiment of inhibition percentage of Apa was measured by the generating rate of metabolite in the presence of 100 μM Apa (study group) compared with no inhibitor (control group). In the experiment of IC 50 determination, the concentration of Apa was set as 0.01, 0.1, 1, 10, 50 and 100 μM, while that of Ven was 100 μM, which is close to its K m value . In the experiment of determining the inhibitory effect of Apa on Ven in RLM and HLM, the concentration of Apa was designed at 0, 2, 5 and 10 μM according to the IC 50 value, while the concentration of Ven was designed at 25, 50, 100, 200 μM according to the K m value.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Bao

Wen

Lin

et al. 2018

Basic Clin Pharma Tox

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The objective of this study was to evaluate the effect of apatinib on the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in SD rats and the inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes. Twenty-one SD male rats were randomly divided into three groups (n = 7): group A (multiple dose of 40 mg/kg apatinib for 7 days), group B (single dose of 40 mg/kg apatinib) and group C (the control group). All samples were measured by UPLC-MS/MS. The results indicated that a single dose of apatinib increased the AUC , AUC and C of both venlafaxine and O-desmethylvenlafaxine significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC and CLz/F of venlafaxine were changed, while no parameters of O-desmethylvenlafaxine were altered. In addition, apatinib was determined to be a mixed inhibitor of venlafaxine.

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“…Rats were randomly divided into two groups: group A and group B (six rats per group). Rats in group A were orally given VEN at 20 mg/kg and in group B were given VEN at 20 mg/kg and FLX at 10 mg/kg . All drugs were given by gastric gavages after 12 h food deprivation.…”

Section: Methodsmentioning

confidence: 99%

“…Hefner et al reported that melperone has a clinically relevant inhibitory potential on CYP2D6 thus increasing the serum concentrations of VEN and decreasing the metabolic ratios of ODVEN/VEN. Zhan et al demonstrated that an intake of apigenin could increase VEN plasma levels and some of its pharmacokinetic parameters (AUC, T max ). Therefore, the potential toxic concentration of VEN can be caused by reduced metabolic capacity .…”

Section: Introductionmentioning

confidence: 99%

Rapid solid‐phase extraction coupled with GC–MS method for the determination of venlafaxine in rat plasma: Application to the drug–drug pharmacokinetic interaction study of venlafaxine combined with fluoxetine

Song

Zheng

Liang

et al. 2017

J of Separation Science

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A rapid and sensitive gas chromatography with mass spectrometry method for the determination of venlafaxine in rat plasma has been developed and applied to a drug-drug interaction study of fluoxetine on pharmacokinetics of venlafaxine in rats. Rat plasma was spiked with 2% aqueous ammonia before subjected to preactivated C solid-phase extraction columns and eluted with methanol. No endogenous interferences were observed under optimal condition. The calibration curve was linear (R = 0.9994) in the range of 10-1000 ng/mL. The quantification limit of venlafaxine in rat plasma was 10 ng/mL. The accuracy was in the range of 85-110%, and the extraction recovery was no less than 50%. Both the intra- and interday precision were 5.0-10.7%. The concentration-time curve showed that plasma concentrations of the coadministration group (group B) were higher than that of single dose group (group A). Both values of C (0.069 mg/L) and AUC (0.291 mg h/L) in group B were statistically greater than that of C (0.046 mg/L) and AUC (0.181 mg·h/L) in group A (P < 0.05). The results indicated that a significant effect of fluoxetine was shown on the pharmacokinetics of venlafaxine, suggesting that drug-drug interactions are of concern for the treatment of depression with the combined use of venlafaxine and fluoxetine.

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Inhibitory Effect of Apigenin on Pharmacokinetics of Venlafaxine in vivo and in vitro

Cited by 11 publications

References 23 publications

Inhibitory Effect of Apigenin on Losartan Metabolism and CYP2C9 Activity in vitro

Inhibitory Effect of Apigenin on Losartan Metabolism and CYP2C9 Activity in vitro

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

Rapid solid‐phase extraction coupled with GC–MS method for the determination of venlafaxine in rat plasma: Application to the drug–drug pharmacokinetic interaction study of venlafaxine combined with fluoxetine

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