Effects of dexamethasone to reverse decreased hepatic midazolam metabolism in rats with acute renal failure

Doi, Masami; Kajikawa, Noriko; Aiba, Tetsuya

doi:10.1080/00498254.2019.1655680

Cited by 8 publications

(9 citation statements)

References 35 publications

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“…In the RECOVERY trial, there was a significant risk reduction for patients requiring supplemental oxygen or being ventilated compared to the usual care group [72]. Dexamethasone is both an inducer and a substrate for the CYP3A4 enzyme [73,74]. Decreased metabolism of dexamethasone may lead to corticosteroid-related acute adverse effects such as hyperglycemia and fluid retention [75].…”

Section: Corticosteroidsmentioning

confidence: 99%

“…Benzodiazepine drugs are largely a CYP3A4 substrate, which suggests potential diseasedrug interactions with this class of drugs. Midazolam is commonly used in producing sedation and is metabolized by CYP3A4 [73]. Most of these medications can be very harmful if the plasma levels are increased following lack of metabolism by inflammation-mediated CYP3A4 or CYP2B6 suppression.…”

Section: Supportive Medicationsmentioning

confidence: 99%

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Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients

Deb

Arrighi

2021

Eur J Drug Metab Pharmacokinet

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Coronavirus Disease 2019 (COVID-19) has been a global health crisis since it was first identified in December 2019. In addition to fever, cough, headache, and shortness of breath, an intense increase in immune response-based inflammation has been the hallmark of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) virus infection. This narrative review summarizes and critiques pathophysiology of COVID-19 and its plausible effects on drug metabolism and disposition. The release of inflammatory cytokines (e.g., interleukins, tumor necrosis factor α), also known as ‘cytokine storm’, leads to altered molecular pathophysiology and eventually organ damage in the lung, heart, and liver. The laboratory values for various liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin) have indicated potential hepatocellular injury in COVID-19 patients. Since the liver is the powerhouse of protein synthesis and the primary site of cytochrome P450 (CYP)-mediated drug metabolism, even a minor change in the liver function status has the potential to affect the hepatic clearance of xenobiotics. It has now been well established that extreme increases in cytokine levels are common in COVID-19 patients, and previous studies with patients infected with non-SARS-CoV-2 virus have shown that CYP enzymes can be suppressed by an infection-related cytokine increase and inflammation. Alongside the investigational COVID-19 drugs, the patients may also be on therapeutics for comorbidities; especially epidemiological studies have indicated that individuals with hypertension, hyperglycemia, and obesity are more vulnerable to COVID-19 than the average population. This complicates the drug-disease interaction profile of the patients as both the investigational drugs (e.g., remdesivir, dexamethasone) and the agents for comorbidities can be affected by compromised CYP-mediated hepatic metabolism. Overall, it is imperative that healthcare professionals pay attention to the COVID-19 and CYP-driven drug metabolism interactions with the goal to adjust the dose or discontinue the affected drugs as appropriate.

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Section: Corticosteroidsmentioning

confidence: 99%

Section: Supportive Medicationsmentioning

confidence: 99%

Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients

Deb

Arrighi

2021

Eur J Drug Metab Pharmacokinet

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“…With livers freshly procured from 5 rats, the microsomes were prepared in a conventional manner with ultra-centrifugation, as previously reported. 24) During the liver procurement, blood was drawn from the inferior vena cava to collect the plasma specimen to be used in the above-mentioned assessments of the plasma AGP level and the plasma unbound fraction of NTG. The protein content of the prepared microsomes was determined with a commercially available protein assay kit (Bio-Rad, Hercules, CA, U.S.A.).…”

Section: Evaluation Of Plasma Unbound Fraction Of Ntg In Control and mentioning

confidence: 99%

Acute Peripheral Inflammation Increases Plasma Concentration of Hypoglycemic Agent Nateglinide with Decreased Hepatic Drug-Metabolizing Activity in Rats

Kojina

Suzuki

Nishiwaki

et al. 2021

Biological & Pharmaceutical Bulletin

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“…Dexamethasone binds and activates the glucocorticoid receptors which mediate alterations in the gene expression. 101 Genetic variation in genes AL-EITAN AND ALAHMAD -9 of 13 implicated in the metabolizing-related genes such as CYP3A7, CYP3A5 and CYP3A4 could affect the corticosteroids response. 102 Moreover, receptor binding genes including Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) and Corticotropin-Releasing Hormone Receptor 1 (CRHR1), and transporters such as ABCB1 are also involved in the corticosteroid's response.…”

Section: Dexamethasonementioning

confidence: 99%

“…Dexamethasone administration could be mediated either intramuscular or intravenous. Dexamethasone binds and activates the glucocorticoid receptors which mediate alterations in the gene expression 101 . Genetic variation in genes implicated in the metabolizing‐related genes such as CYP3A7, CYP3A5 and CYP3A4 could affect the corticosteroids response 102 .…”

Section: Pharmacogenomics Of Drug Metabolising Genesmentioning

confidence: 99%

Pharmacogenomics of genetic polymorphism within the genes responsible for SARS‐CoV‐2 susceptibility and the drug‐metabolising genes used in treatment

AL-Eitan

Alahmad

2020

Reviews in Medical Virology

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Summary The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) represents a significant challenge to international health. Pharmacogenomics aims to identify the different genetic variations that exist between individuals and populations in order to determine appropriate treatment protocols to enhance the efficacy of drugs and reduce their side‐effects. This literature review provides an overview of recent studies of genetic polymorphisms in genes that mediate the SARS‐CoV‐2 infection mechanism (ACE1, ACE2, TMPRSS2 and CD26). In addition, genetic variations in the drug‐metabolising enzyme genes of several selected drugs used in the treatment of COVID‐19 are summarised. This may help construct an effective health protocol based on genetic biomarkers to optimise response to treatment. Potentially, pharmacogenomics could contribute to the development of effective high‐throughput assays to improve patient evaluation, but their use will also create ethical, medical, regulatory, and legal issues, which should now be considered in the era of personalised medicine.

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Effects of dexamethasone to reverse decreased hepatic midazolam metabolism in rats with acute renal failure

Cited by 8 publications

References 35 publications

Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients

Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients

Acute Peripheral Inflammation Increases Plasma Concentration of Hypoglycemic Agent Nateglinide with Decreased Hepatic Drug-Metabolizing Activity in Rats

Pharmacogenomics of genetic polymorphism within the genes responsible for SARS‐CoV‐2 susceptibility and the drug‐metabolising genes used in treatment

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