In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats

Varghese, Alice; Savai, Jay; Mistry, Shruti; Khandare, Preeti; Barve, Kalyani; Pandita, Nancy; Gaud, Ram

doi:10.2174/1872312810666160219121415

Cited by 3 publications

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“…In correlation to this, we have further studied the in vitro CYP2D inhibition potential of T. arjuna extracts in RLM and the influence of the aqueous bark extract of T. arjuna on the oral pharmacokinetics and pharmacodynamics of metoprolol succinate in rats. These studies showed that the aqueous bark extract of T. arjuna led to a significant reduction (p < 0.05) in AUC 0‐24h and C max of metoprolol succinate in rats and a further reduction in the pharmacodynamic activity (Varghese et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Despite understanding the immense potency and ability of T. arjuna as a cardioprotective agent, there is a lack of information on its interaction with cytochrome enzymes. Previously, we reported the in vitro CYP1A and CYP2D interaction of T. arjuna extracts in rat liver microsomes and also the in vitro modulatory effects of Terminalia arjuna , arjunic acid, arjunetin and arjungenin on CYP3A, CYP2D and CYP2C9 enzyme activity in human liver microsomes (Varghese et al, ). These findings suggest that there are some constituents in T. arjuna that are responsible for the inhibitory activity.…”

Section: Introductionmentioning

confidence: 90%

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Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for its CYP3A and CYP2D inhibition in rat liver microsomes

Varghese

Saboo

Wairkar

2018

Biopharm & Drug Disp

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Terminalia arjuna (T. arjuna) is an Indian medicinal plant belonging to the family Combretaceae and possesses numerous therapeutic activities including its immense cardioprotective activity. In the present work, a methanolic bark extract of T. arjuna was evaluated for CYP3A and CYP2D inhibition potential in rat liver microsomes (RLM). Further, the methanolic bark extract was fractionated successively using increasing polarity solvents starting with petroleum ether, chloroform, ethyl acetate and n-butanol. The fractions so obtained were also evaluated for their CYP3A and CYP2D inhibition potential. Probe substrates testosterone and dextromethorphan were used for CYP3A and CYP2D respectively. The IC values for the methanolic extract and the fractions were found to be less than 50 μg/ml in RLM for both CYP3A and CYP2D isoenzymes. The most potent n-butanol fraction was further fractionated with column chromatography to isolate the highest active constituent responsible for the activity. Fraction 4 of the n-butanol extract was the most potent fraction with IC values of 5.64 ± 0.735 μg/ml and 16.63 ± 0.879 μg/ml for CYP3A and CYP2D in RLM, respectively. Therefore, in vitro data indicated that the Terminalia arjuna extract contains constituents that can potentially inhibit the CYP3A and CYP2D isoenzymes which may in turn lead to pharmacokinetic drug-herb interaction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for its CYP3A and CYP2D inhibition in rat liver microsomes

Varghese

Saboo

Wairkar

2018

Biopharm & Drug Disp

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Herb-Drug Interactions and Their Impact on Pharmacokinetics: An Update

Cheng

Xia

et al. 2023

CDM

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Herb medicine has a long history of application and is still used worldwide. With the development of complementary and alternative medicine, the interaction between herb and drugs has attracted more and more attention. Herb-drug interactions (HDI) could cause decreased efficiency, increased toxicity, and affect the drug absorption and disposition processes due to the interference of their pharmacological or pharmacokinetic effects. Hence, the mechanisms and results of herb-pharmacokinetic interactions should be comprehensively summarized. Here, we have summarized the mechanisms of HDI and pharmacokinetic interactions in the last ten years based on searching on PubMed, Science Direct, and Web of Science with different keywords. Besides, the pharmacokinetic interactions were related to nine commonly used herbs and drugs, including Ginseng, Salvia miltiorrhiza, Ginkgo biloba, Garlic, Coptis chinensis, St. John's wort, Ginger, Licorice, Silythistle and Fructus Schisandrae. This review provides an overview of HDI to provide a reference for the rational and safe clinical use of herbs and drugs.

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Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs

Chen

Bai

Wang

et al. 2020

CPB

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Background: Chiral safety, especially chiral drug inversion in vivo, is the top priority of current scientific research. Medicine researchers and pharmacists often ignore that one enantiomer will be converted or partially converted to another enantiomer when it is ingested in vivo. So that, in the context that more than 50% of the listed drugs are chiral drugs, it is necessary and important to pay attention to the inversion of chiral drugs. Methods: The metabolic and stereoselective pharmacokinetic characteristics of seven chiral drugs with one chiral center in hydroxy group were reviewed by in vivo and in vitro include the possible chiral inversion of each drug enantiomer. These seven drugs include (S)-Mandelic acid, RS-8359, Tramadol, Venlafaxine, Carvedilol, Fluoxetine and Metoprolol. Results: The differences in stereoselective pharmacokinetic could be found for all the seven chiral drugs, since R and S isomers often exhibit different PK and PD properties. However, not every drug has shown the properties of one direction or two direction chiral inversion. For chiral hydroxyl group drugs, the redox enzyme system may be one of the key factors for chiral inversion in vivo. Conclusion: In vitro and in vivo chiral inversion is a very complex problem and may occur during every process of ADME. Nowadays, research on chiral metabolism in the liver has the most attention, while neglecting the chiral transformation of other processes. Our review may provide basis for the drug R&D and the safety of drugs in clinical therapy.

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In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats

Abstract: Based on our in vitro and in vivo findings and until further clinical drug interaction experiments are conducted, the co-administration of drugs, especially those primarily cleared via CYP2D catalyzed metabolism, with T. arjuna extracts should be done with caution.

Cited by 3 publications

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Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for its CYP3A and CYP2D inhibition in rat liver microsomes

Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for its CYP3A and CYP2D inhibition in rat liver microsomes

Herb-Drug Interactions and Their Impact on Pharmacokinetics: An Update

Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs

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