Development and Palatability Assessment of Norvir® (Ritonavir) 100 mg Powder for Pediatric Population

Morris, John B.; Tisi, David A.; Tan, David Cheng Thiam; Worthington, Jeffrey H.

doi:10.3390/ijms20071718

Cited by 16 publications

(11 citation statements)

References 17 publications

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“…These have shown efficacy in viral respiratory tract infections [26] and have been demonstrated to increase the cough threshold against a single-inhalation capsaicin challenge [27] , [28] . In addition, peanut butter or fruit concentrate have been demonstrated to improve the tolerability of other bitter agents such as ritonavir suspension [29] . Pre-administration of such treatments/food substances prior to HCQ administration by nebulisation is therefore recommended, where possible.…”

Section: Targeted Delivery Of Hydroxychloroquine To the Lung Via Oralmentioning

confidence: 99%

Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19

et al. 2020

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Current formulations and dose regimens of hydroxychloroquine (HCQ) put patients at risk of harm. An analysis of clinical trials registered on ClinicalTrials.gov revealed that this may continue as many studies combine HCQ with agents that prolong the QT interval. Further, almost all of the trials registered do not consider dosage adjustment in the elderly, a patient population most likely to require HCQ treatment. Here we describe an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma and discuss how this approach may reduce side-effects and improve efficacy. As this simple formulation progressed to phase II studies, safety data can be used to immediately enable phase II trials in COVID-19.

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Section: Targeted Delivery Of Hydroxychloroquine To the Lung Via Oralmentioning

confidence: 99%

Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19

et al. 2020

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“…However, all of these drugs show limited oral absorption [67][68][69][70][71][72] due to poor biopharmaceutical or pharmacokinetic properties. Namely, QSPR predictions indicate that all six drugs are substrates for P-gp efflux transporters, in addition to low passive permeability of ritonavir, dipyridamole and thymopentin, and first pass metabolism of montelukast, ritonavir, lopinavir, dipyridamole and telmisartan.…”

Section: Pbpk Prediction Resultsmentioning

confidence: 99%

An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

Djoković

Djikić

Cvijić

et al. 2021

Molecular Informatics

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Aims: An infectious disease caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we investigated an integrative in silico drug repurposing approach as a valuable tool for rapid selection of potential candidates against SARS-CoV-2 Main Protease (M pro ). Main methods:To screen FDA-approved drugs, we designed an integrative in silico drug repurposing approach implementing structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data-mining analysis of drug-gene-COVID-19 association. Key findings:Through the presented approach, 43 candidates with potential inhibitory effect on M pro were selected and further evaluated according to the predictions of tissue disposition, drug-gene-COVID-19 associations and potential pleiotropic effects. We singled out 9 FDA approved drugs as the most promising for their profiling in COVID-19 drug discovery campaigns. Our results were in agreement with current experimental findings, which validate the applied integrative approach and may support clinical decisions for a novel epidemic wave of COVID-19.Significance: To the best of our knowledge, this is the first integrative in silico repurposing study for COVID-19 with a clear advantage in linking structure-based molecular modeling of M pro inhibitors with predictions of tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.

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“…However, all of these drugs show limited oral absorption [67][68][69][70][71][72] into kidneys and lungs. 72,74 These data support the value of in silico simulation results, and…”

Section: Pbpk Prediction Resultsmentioning

confidence: 99%

An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

Djoković¹,

Djikić²,

Cvijić³

et al. 2020

Preprint

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<div><b>Aims</b>: An infectious disease (COVID-19) caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we investigated an integrative in silico drug repurposing approach as a valuable tool for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro).</div><div><br></div><div><b>Main methods:</b> To screen FDA-approved drugs, we designed an integrative in silico drug repurposing approach implementing structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data-mining analysis of drug-gene-COVID-19 association.</div><div><br></div><div><b>Key findings:</b> Through the presented approach, 43 candidates with potential inhibitory effect on Mpro were selected and further evaluated according to the predictions of tissue disposition, drug-gene-COVID-19 associations and potential pleiotropic effects. We singled out 9 FDA approved drugs as the most promising for their profiling in COVID-19 drug discovery campaigns. Our results were in agreement with current experimental findings, which validate the applied integrative approach and may support clinical decisions for a novel epidemic wave of COVID-19.</div><div><br></div><div><b>Significance:</b> To the best of our knowledge, this is the first integrative in silico repurposing study for COVID-19 with a clear advantage in linking structure-based molecular modeling of Mpro inhibitors with predictions of tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.</div>

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Development and Palatability Assessment of Norvir® (Ritonavir) 100 mg Powder for Pediatric Population

Cited by 16 publications

References 17 publications

Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19

Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19

An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

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