Genetic variations and epigenetic modulations in CYP genes: Implications in NSAID-treatment of arthritis patients

Chowdhury, Shalini Roy; Gupta, Oindrilla Dutta; Ghosh, Arnab; Singha, Partha Sarathi; Firdaus, Syed Benazir; Klarskov, Klaus

doi:10.1007/s13237-021-00373-0

Cited by 2 publications

(3 citation statements)

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“…In the present collection of articles, Chowdhury et al talks about the importance of cytochrome P450 (CYP) and emphasized how it's polymorphic variants can affect the metabolism of nonsteroidal antiinflammatory drugs (NSAIDs). In the context of epimutagenic mechanisms discussed in this review like regulatory role of miRNA(s) in CYP expression; it was interesting to learn how H3K27ac modulates the binding of mediator complex subunit 25 (MED-25), thereby regulating the expression of CYP variant (2C9) in humans [11].…”

Section: Epimutagenesismentioning

confidence: 99%

Impact of epigenetics on human health and possible tool for remediation

Paul

2021

Nucleus

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Section: Epimutagenesismentioning

confidence: 99%

Impact of epigenetics on human health and possible tool for remediation

Paul

2021

Nucleus

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“…It is established at in vitro / in vivo (preclinical/clinical) levels that inflammatory cytokines alter cytochrome P450 (CYP) expressions, which can lead to severe consequences. , CYPs are responsible for the biotransformation of drugs. A combination of antiarthritic drugs like disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs) is used simultaneously to curb the disease pathophysiology and signs/symptoms of RA, respectively. In addition, multiple drugs are used to tackle several comorbidities of RA patients .…”

Section: Introductionmentioning

confidence: 99%

“… 6 , 7 CYPs are responsible for the biotransformation of drugs. A combination of antiarthritic drugs like disease-modifying antirheumatic drugs (DMARDs) 8 and nonsteroidal anti-inflammatory drugs (NSAIDs) 9 is used simultaneously to curb the disease pathophysiology and signs/symptoms of RA, respectively. In addition, multiple drugs are used to tackle several comorbidities of RA patients.…”

Section: Introductionmentioning

confidence: 99%

EIDD-1931 Treatment Tweaks CYP3A4 and CYP2C8 in Arthritic Rats to Expedite Drug Interaction: Implication in Oral Therapy of Molnupiravir

Bhardwaj,

Kour,

Rai

et al. 2024

ACS Omega

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EIDD-1931 is the active form of molnupiravir, an orally effective drug approved by the United States Food and Drug Administration (USFDA) against COVID-19. Pharmacokinetic alteration can cause untoward drug interaction (drug−drug/ disease−drug), but hardly any information is known about this recently approved drug. Therefore, we first investigated the impact of the arthritis state on the oral pharmacokinetics of EIDD-1931 using a widely accepted complete Freund's adjuvant (CFA)induced rat model of rheumatoid arthritis (RA) after ascertaining the disease occurrence by paw swelling measurement and X-ray examination. Comparative oral pharmacokinetic assessment of EIDD-1931 (normal state vs arthritis state) showed that overall plasma exposure was augmented (1.7-fold) with reduced clearance (0.54-fold), suggesting its likelihood of dose adjustment in arthritis conditions. In order to elucidate the effect of EIDD-1931 treatment at a therapeutic regime (normal state vs arthritis state) on USFDA-recommended panel of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) for drug interaction using the same disease model, we monitored protein and mRNA expressions (rat homologs) in liver tissue by western blotting (WB) and real time-polymerase chain reaction (RT-PCR), respectively. Results reveal that EIDD-1931 treatment could strongly influence CYP3A4 and CYP2C8 among experimental proteins/mRNAs. Although CYP2C8 regulation upon EIDD-1931 treatment resembles similar behavior under the arthritis state, results dictate a potentially reverse phenomenon for CYP3A4. Moreover, the lack of any CYP inhibitory effect by EIDD-1931 in human/rat liver microsomes (HLM/ RLM) helps to ascertain EIDD-1931 treatment-mediated disease−drug interaction and the possibility of drug−drug interaction with disease-modifying antirheumatic drugs (DMARDs) upon coadministration. As elevated proinflammatory cytokine levels are prevalent in RA and nuclear factor-kappa B (NF-kB) and nuclear receptors control CYP expressions, further studies should focus on understanding the regulation of affected CYPs to subside unexpected drug interaction.

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Genetic variations and epigenetic modulations in CYP genes: Implications in NSAID-treatment of arthritis patients

Cited by 2 publications

References 129 publications

Impact of epigenetics on human health and possible tool for remediation

Impact of epigenetics on human health and possible tool for remediation

EIDD-1931 Treatment Tweaks CYP3A4 and CYP2C8 in Arthritic Rats to Expedite Drug Interaction: Implication in Oral Therapy of Molnupiravir

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