Enantioselective inhibition of Cytochrome P450-mediated drug metabolism by a novel antithrombotic agent, S002-333: Major effect on CYP2B6

Bhateria, Manisha; Ramakrishna, Rachumallu; Puttrevu, Santosh Kumar; Saxena, Anil Kumar; Bhatta, Rabi Sankar

doi:10.1016/j.cbi.2016.07.001

Cited by 11 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Effect of IS01957 on inhibition of CYP2C9 was executed in the concentration range of 0–25 μM using substrate concentration of 5 μM which was based on the preliminary results to determine Km which matched with the previous literature (Arora et al, ; Bhateria et al, ). Sulfaphenazole was used as positive control to elucidate the validity of the probe reactions and IC 50 was found to be 0.41 μM which is in good agreement with the reported results (Arora et al, ; Bhateria et al, ). IS01957 displayed the IC 50 of 18.14 μM for the impediment of CYP2C9 mediated marker reaction.…”

Section: Resultsmentioning

confidence: 92%

See 1 more Smart Citation

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

Sharma

Gour

Bhatt

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

Diclofenac is one of the world's largest selling nonsteroidal anti‐inflammatory drugs. The major concerns related to oral diclofenac therapy are gastrointestinal and cardiovascular side effects for which explicitly emphasis has been given to use it at lowest effective dose for the shortest duration. On the other hand, IS01957 has been designed under the purview of anti‐inflammatory drug and bioavailability enhancer. IS01957 have dual action on inflammation and nociception with acceptable safety profile. In the quest for a suitable combination with improved therapeutic efficacy and better tolerability, pharmacodynamic and pharmacokinetic interaction studies were performed for diclofenac with or without IS01957 in mice model. Results showed that IS01957 enhanced both anti‐inflammatory effect and plasma concentration of diclofenac upon concomitant oral administration. These interesting results steered to enumerate the possible role of IS01957 towards diclofenac pharmacokinetics through a panel of mechanistic investigations: (a) BCRP dependent ATPase activity was markedly interfered by IS01957; (b) IS01957 increased the intestinal permeability of diclofenac in the single pass in‐situ perfusion model; (c) IS01957 inhibited the CYP2C9 catalyzed diclofenac 4‐hydroxylation in human liver microsomes. Immunoblotting results suggest that diclofenac action was improved significantly in the presence of IS01957 involving MAPK pathways. Finally acute gastric damage study showed that IS01957 in combination with diclofenac was better to improve the desired PGE2 level as compare to alone. In nutshell, IS01957 have potential to augment the efficacy of diclofenac through pharmacokinetic modulation. Further investigations are required for dose reduction of diclofenac to combat its liabilities before going into clinical setting.

show abstract

Section: Resultsmentioning

confidence: 92%

“…The study was performed using sulfaphenazole as a standard inhibitor. Rate of metabolite formation was calculated where reaction mixture without inhibitor was considered as control and IC 50 was determined using GraphPad Prism software (Arora et al, ; Bhateria, Ramakrishna, Puttrevu, Saxena, & Bhatta, ).…”

Section: Methodsmentioning

confidence: 99%

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

Sharma

Gour

Bhatt

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…To assess the potential of PI to cause DDI by inhibiting the major human CYP450 enzymes, probe substrates specific for each enzyme in a reversible and time-dependent manner were used to assay the activity of each CYP450 enzyme in HLM in the presence and absence of PI (Table 1; Bhateria et al, 2016;Ghosal et al, 2011;Ramirez et al, 2004). In this assay, the activities of the nine recombinant human …”

Section: Assessment Of the Potential Of Pi To Inhibit Cyp450 Enzymesmentioning

confidence: 99%

“…The MRM transitions, fragment voltage and collision energy of the substrate probes are summarized inTable 1(Bhateria et al, 2016;Ghosal et al, 2011;Ramirez et al, 2004).HPLC-MS, MS/MS and MS/MS/MS were jointly used to identify the chemical structures of the metabolites. The metabolites were identified based on the accurate determination of their masses and fragmentation patterns in positive mode.…”

mentioning

confidence: 99%

“…Hepatocytes were treated with PI(1, 10, and 100 μM) or the positive control inducers omeprazole (100 μM), phenobarbital (750 μM) or rifampin (10 μM) once a day for three consecutive days(Bhateria et al, 2016;Paris et al, 2009). The induction of CYP450 enzyme activity was assessed using a microsomal assay with the selective probe substrates phenacetin (80 μM), bupropion (50 μM) and testosterone (250 μM) for CYP1A2, CYP2B6 and CYP3A4 catalytic activities, respectively.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes

Tan

Dong

Zhang

et al. 2017

Biomedical Chromatography

View full text Add to dashboard Cite

Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques were used to estimate the enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC > 100 μm). In the induction studies, PI had minimal effects on CYP1A2, CYP2B6and CYP3A4 activity. Based on these results, PI would not be expected to cause clinically significant CYP450 inhibition or induction.

show abstract

Subterminal hydroxyeicosatetraenoic acids: Crucial lipid mediators in normal physiology and disease states

Shoieb

El-Sherbeni

El‐Kadi

2019

Chemico-Biological Interactions

View full text Add to dashboard Cite

Enantioselective inhibition of Cytochrome P450-mediated drug metabolism by a novel antithrombotic agent, S002-333: Major effect on CYP2B6

Cited by 11 publications

References 41 publications

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes

Subterminal hydroxyeicosatetraenoic acids: Crucial lipid mediators in normal physiology and disease states

Contact Info

Product

Resources

About