GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Table1.DOCX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 13 ( 2023-1-6)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2023-1-6)
    Abstract: The aim of this study is to investigate the effects of CYP3A4 genetic polymorphisms on the metabolism of cyclosporine (CsA) in vitro and identify drugs that interact with CsA. An enzymatic incubation system was developed to evaluate the kinetic parameters of CYP3A4 on CsA catalysis. A total of 132 drugs were screened to identify potential drug–drug interactions. Sprague–Dawley rats were used to determine the interaction between CsA and nimodipine and nisoldipine. The metabolite AM1 was measured by ultra-performance liquid chromatography–tandem mass spectrometry. The results demonstrate that 16 CYP3A4 variants (CYP3A4.7, 8, 9, 12, 13, 14, 16, 18, 19, 23, 24, 28, 31, 32, 33, and 34) have a lower metabolic capacity for CsA, ranging from 7.19% to 72.10%, than CYP3A4.1. In contrast, the relative clearance rate of CYP3A4.5 is significantly higher than that of CYP3A4.1. Moreover, CYP3A4.20 loses its catalytic ability, and five other variants have no significant difference. A total of 12 drugs, especially calcium channel blockers, were found to remarkably inhibit the metabolism of CsA with an inhibitory rate of over 80%. Nimodipine inhibits the activity of CsA in rat liver microsomes with an IC 50 of 20.54 ± 0.93 μM, while nisoldipine has an IC 50 of 16.16 ± 0.78 μM. In in vivo , three groups of Sprague–Dawley rats were administered CsA with or without nimodipine or nisoldipine; the AUC (0-t) and AUC (0-∞) of CsA were significantly increased in the nimodipine group but not obviously in the nisoldipine group. Mechanistically, the inhibition mode of nimodipine on cyclosporine metabolism is a mixed inhibition. Our data show that gene polymorphisms of CYP3A4 and nimodipine remarkably affect the metabolism of CsA, thus providing a reference for the precise administration of CsA.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.1044817
    DOI: 10.3389/fphar.2022.1044817.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    DataSheet1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-9-2)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-9-2)
    Abstract: 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 IC 50 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 C max 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.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.985159
    DOI: 10.3389/fphar.2022.985159.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    The effect of CYP3A4 genetic polymorphism and drug interaction on the metabolism of istradefylline
    Elsevier BV ; 2022
    In:  Chemico-Biological Interactions Vol. 366 ( 2022-10), p. 110123-
    Details
    In: Chemico-Biological Interactions, Elsevier BV, Vol. 366 ( 2022-10), p. 110123-
    Type of Medium: Online Resource
    ISSN: 0009-2797
    URL: Article
    DOI: 10.1016/j.cbi.2022.110123
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1496834-4
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Effects of dietary flavonoids on the metabolism of vortioxetine and its potential mechanism
    Bentham Science Publishers Ltd. ; 2023
    In:  Current Medicinal Chemistry Vol. 30 ( 2023-06-07)
    Details
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 30 ( 2023-06-07)
    Abstract: Quercetin and apigenin are two common dietary flavonoids widely found in foods and fruits. Quercetin and apigenin can act as the inhibitors of CYP450 enzymes, which may affect the pharmacokinetics of clinical drugs. Vortioxetine (VOR), approved for marketing by the Food and Drug Administration (FDA) in 2013, is a novel clinical drug for treating major depressive disorder (MDD). Objective: This study aimed to evaluate the effects of quercetin and apigenin on the metabolism of VOR in in vivo and in vitro experiments. Method: Firstly, 18 Sprague-Dawley rats were randomly divided into three groups: control group (VOR), group A (VOR + 30 mg/kg quercetin) and group B (VOR + 20 mg/kg apigenin). We collected the blood samples at different time points before and after the final oral administration of 2 mg/kg VOR. Subsequently, we further used rat liver microsomes (RLMs) to investigate the half-maximal inhibitory concentration (IC50) of the metabolism of vortioxetine. Finally, we evaluated the inhibitory mechanism of two dietary flavonoids on VOR metabolism in RLMs. Results: In animal experiments, we found AUC (0-∞) (area under the curve from 0 to infinity) and CLz/F (clearance) to be obviously changed. Compared to controls, AUC (0-∞) of VOR in group A and group B was 2.22 and 3.54 times higher, respectively, while CLz/F of VOR in group A and group B was significantly decreased down to nearly two-fifth and one-third. In in vitro studies, the IC50 value of quercetin and apigenin in the metabolic rate of vortioxetine was 5.322 μM and 3.319 μM, respectively. Ki value of quercetin and apigenin was found to be 0.279 and 2.741, respectively, and the αKi value of quercetin and apigenin was 0.066 and 3.051 μM, respectively. Conclusion: Quercetin and apigenin exhibited inhibitory effects on the metabolism of vortioxetine in vivo and in vitro. Moreover, quercetin and apigenin non-competitively inhibited the metabolism of VOR in RLMs. Thus, we should pay more attention to the combination between these dietary flavonoids and VOR in the future clinical use.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    URL: Article
    DOI: 10.2174/0929867330666230607104411
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    The effect of anlotinib on the pharmacokinetic profile of oxycodone and the underlying mechanism
    Elsevier BV ; 2022
    In:  Chemico-Biological Interactions Vol. 364 ( 2022-09), p. 110044-
    Details
    In: Chemico-Biological Interactions, Elsevier BV, Vol. 364 ( 2022-09), p. 110044-
    Type of Medium: Online Resource
    ISSN: 0009-2797
    URL: Article
    DOI: 10.1016/j.cbi.2022.110044
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1496834-4
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Inhibitory effects of fluoxetine and duloxetine on the pharmacokinetics of metoprolol in vivo and in vitro
    Wiley ; 2022
    In:  Fundamental & Clinical Pharmacology Vol. 36, No. 6 ( 2022-12), p. 1057-1065
    Details
    In: Fundamental & Clinical Pharmacology, Wiley, Vol. 36, No. 6 ( 2022-12), p. 1057-1065
    Abstract: Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases the possibility of drug interaction. Simultaneously compare the effects of duloxetine and fluoxetine on metoprolol metabolism, and provide evidence‐based guidance for medication safety. Sprague–Dawley rats were randomly divided into three groups: group A (10.3 mg/kg metoprolol alone), group B (10.3 mg/kg metoprolol + 6.2 mg/kg fluoxetine), and group C (10.3 mg/kg metoprolol + 6.2 mg/kg duloxetine). Tail vein blood was collected and subjected to the ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) detection. Moreover, in vitro inhibition of fluoxetine and duloxetine were assessed by incubating liver microsomes and CYP2D6.1 with metoprolol. In in vivo study, the administration of fluoxetine or duloxetine significantly increased the AUC (0− 𝑡 ) and AUC (0−∞) of metoprolol ( P   〈  0.05). Differences between fluoxetine and duloxetine in plasma concentration were also investigated, and their pharmacokinetic parameters such as AUC (0− 𝑡 ) and AUC (0−∞) were significantly distinct ( P   〈  0.05). In vitro, fluoxetine and duloxetine inhibited the metabolism of metoprolol via mixed competitive mechanism of cytochrome P450. IC 50 values of fluoxetine and duloxetine were 12.86 and 2.51 μM, respectively. Moreover, the metabolism rate of metoprolol was inhibited to 19.62% and 17.14% in recombinant human CYP2D6.1 by fluoxetine and duloxetine, respectively. Duloxetine showed a more significant inhibitory potential compared to fluoxetine in vitro, but the main pharmacokinetic parameters of fluoxetine and duloxetine revealed differences in inhibiting metoprolol metabolism in vivo.
    Type of Medium: Online Resource
    ISSN: 0767-3981 , 1472-8206
    URL: Issue
    URL: Article
    DOI: 10.1111/fcp.v36.6
    DOI: 10.1111/fcp.12795
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2006242-4
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    DataSheet1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-3-10)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-10)
    Abstract: The aim of this study was to 1) investigate the effects of 27 CYP3A4 variants on the metabolism of osimertinib and 2) study the interactions between osimertinib and others as well as the underlying mechanism. A recombinant human CYP3A4 enzymatic incubation system was developed and employed to determine the kinetic profile of CYP3A4 variants. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was applied to detect the concentration of the main metabolite, AZ5104. The results demonstrated that the relative clearance rates of CYP3A4.19, 10, 18, 5, 16, 14, 11, 2, 13, 12, 7, 8, and 17 in catalyzing osimertinib were significantly reduced to a minimum of 25.68% compared to CYP3A4.1, while those of CYP3A4.29, 32, 33, 28, 15, 34, and 3 were obviously enhanced, ranging from 114.14% to 284.52%. The activities of the remaining variants were almost equal to those of CYP3A4.1. In addition, 114 drugs were screened to determine the potential interaction with osimertinib based on the rat liver microsome (RLM) reaction system. Sixteen of them inhibited the production of AZ5104 to 20% or less, especially proton pump inhibitors, among which the IC 50 of rabeprazole was 6.49 ± 1.17 μM in RLM and 20.39 ± 2.32 μM in human liver microsome (HLM), with both following competitive and non-competitive mixed mechanism. In an in vivo study, Sprague–Dawley (SD) rats were randomly divided into groups, with six animals per group, receiving osimertinib with or without rabeprazole, omeprazole, and lansoprazole. We found that the AUC (0–t) , AUC (0–∞) , and C max of osimertinib decreased significantly after co-administration with rabeprazole orally, but they increased remarkably when osimertinib was administered through intraperitoneal injection. Taken together, our data demonstrate that the genetic polymorphism and proton pump inhibitors remarkably influence the disposition of osimertinib, thereby providing basic data for the precise application of osimertinib.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.794931
    DOI: 10.3389/fphar.2022.794931.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...