Ombitasvir/paritaprevir/ritonavir+dasabuvir and ribavirin associated drug-induced liver injury and syndrome of inappropriate secretion of anti-diuretic hormone: A case report

Kumar, Rahul; Hsiang, John; Tan, Jessica; Thurairajah, Prem Harichander

doi:10.3350/cmh.2018.0063

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Its action prevents viral replication by inhibiting the NS3/4A serine protease of HCV; PAR was first available in the market in a fixed-dose combination with ombitasvir, dasabuvir, and ritonavir as an FDA-approved medication (Badri et al., 2016 ). Its common side effects include headache, fatigue, nausea, pruritus, and insomnia, reported in >10% of patients (Kumar et al., 2019 ). Other studies have reported a lack of significant side effects and a short duration of therapy, which are considerable advantages of PAR over other antiviral drugs (Alamri et al., 2020 ; Yaras et al., 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Antivirals virtual screening to SARS-CoV-2 non-structural proteins

Nunes

Paschoal

Costa

et al. 2021

Journal of Biomolecular Structure and Dynamics

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In March 2020, the World Health Organization (WHO) declared coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Since then, the search for a vaccine or drug for COVID-19 treatment has started worldwide. In this regard, a fast approach is the repurposing of drugs, primarily antiviral drugs. Herein, we performed a virtual screening using 22 antiviral drugs retrieved from the DrugBank repository, azithromycin (antibiotic), ivermectin (antinematode), and seven non-structural proteins (Nsps) of SARS-CoV-2, which are considered important targets for drugs, via molecular docking and molecular dynamics simulations. Drug–receptor binding energy was employed as the main descriptor. Based on the results, paritaprevir was predicted as a promising multi-target drug that favorably bound to all tested Nsps, mainly adipose differentiation-related protein (ADRP) (-36.2 kcal mol −1 ) and coronavirus main proteinase (Mpro) (-32.2 kcal mol −1 ). Moreover, the results suggest that simeprevir is a strong inhibitor of Mpro (-37.2 kcal mol −1 ), which is an interesting finding because Mpro plays an important role in viral replication. In addition to drug–receptor affinity, hot spot residues were characterized to facilitate the design of new drug derivatives with improved biological responses.

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Section: Resultsmentioning

confidence: 99%

Antivirals virtual screening to SARS-CoV-2 non-structural proteins

Nunes

Paschoal

Costa

et al. 2021

Journal of Biomolecular Structure and Dynamics

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“…However, in a developing fetus who may be exposed to the drug, it could prove very significant due to the fact that CYP3A7 is the only CYP3A enzyme in the fetal liver and is known to have an average K cat 1/100 that of CYP3A4 for most drug substrates (Li and Lampe, 2019), hence increasing the risk for drug-drug interactions and drug toxicity in the developing fetus and neonate. Post-marketing surveillance revealed instances of sudden alanine aminotransferase elevations and druginduced hepatotoxicity with paritaprevir in combination with other HCV antiviral inhibitors ("Viekira Pak" 2012;Kumar et al 2019). While the mechanism of liver injury is currently unknown, it is possible that reactive metabolites produced from one or more of the drugs in the combination treatment may play a role.…”

Section: Discussionmentioning

confidence: 99%

HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation

Work,

Hackett,

Lampe

2024

Drug Metab Dispos

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The hepatitis C virus (HCV) poses a great risk to pregnant people and their developing fetus, yet no HCV antiviral treatment guidelines have been established. While there has been a substantial increase in the development of HCV antivirals, the effect they have on the developing fetus remains poorly defined. Many of these drugs are metabolized through the cytochrome P450 CYP3A pathway, which is mediated by CYP3A7 in the fetus and developing infant. In this study, we sought to investigate the effect HCV antivirals have on CYP3A7 metabolism, as this CYP enzyme plays a vital role in proper fetal and neonatal development. Of the thirteen HCV antivirals we investigated, eight (~62%) inhibited CYP3A7 metabolic activity by 50% or more at a concentration of 20 µM. Furthermore, paritaprevir, asunaprevir, simeprevir, danoprevir, and glecaprevir all had observed half-maximal inhibitory concentrations between the range of 10-20 µM, which is physiologically relevant in comparison to the K m of DHEA-S oxidation (reported to be between 5 to 20 µM). We also discovered that paritaprevir is a timedependent inhibitor of CYP3A7, which shifts the IC 50 ~2-fold from 11 µM to 5 µM. Upon further characterization, paritaprevir inactivates DHEA-S metabolism by CYP3A7, with K I and K inact values of 4.66 µM and 0.00954 min -1 , respectively. Depending on treatment plan and off-label drug use, HCV treatment could adversely affect the fetal-maternal communication axis by blocking fetal CYP3A7 metabolism of important endogenous hormones.

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“…The underlying mechanism of SIADH and hyponatremia in respiratory viral infections might be neutrophilia and higher concentrations of pro-inflammatory cytokines that activate hypothalamus for release of AVP with subsequent hyponatremia [36] . Likewise, antiviral protease inhibitors ribavirin and paritaprevir therapy may lead to SIADH and hyponatremia [37] .…”

Section: Physiological Profile Of Arginine Vasopressinmentioning

confidence: 99%

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

Al-Kuraishy¹,

Al-Gareeb²,

Qusti

et al. 2021

Biomedicine & Pharmacotherapy

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In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.

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Ombitasvir/paritaprevir/ritonavir+dasabuvir and ribavirin associated drug-induced liver injury and syndrome of inappropriate secretion of anti-diuretic hormone: A case report

Cited by 4 publications

References 11 publications

Antivirals virtual screening to SARS-CoV-2 non-structural proteins

Antivirals virtual screening to SARS-CoV-2 non-structural proteins

HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

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