Population Pharmacokinetics of Remdesivir and GS-441524 in Hospitalized COVID-19 Patients

Leegwater, Emiel; Moes, Dirk Jan A R; Bosma, Liesbeth; Ottens, Thomas H.; Meer, I.M. van der; Nieuwkoop, Cees van; Wilms, E.B.

doi:10.1128/aac.00254-22

Cited by 15 publications

(20 citation statements)

References 33 publications

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“…Although the elimination rate was similar to that in our study, the larger CL and V may be attributed to the high BMI in the study population as the authors suggested. 11 The AUC of GS-441524 was in a similar range as previously reported. 6 In addition, these studies the relationship between GS-441524 exposure and renal function.…”

Section: Discussionsupporting

confidence: 86%

“…In one study, 12 the CL and V of GS‐441524 were reported as 11.8 L/h (ISV = 26%) and 382 L (ISV = 34.5%), respectively, which were similar to our results (11.0 L/h [ISV = 43.0%] and 271 L [ISV = 58.1%], respectively). Another study 11 reported the CL and V of GS‐441524 in patients with COVID‐19 as 27.6 L/h (ISV = 47.4%) and 1060 L (ISV = 42.9), respectively. Although the elimination rate was similar to that in our study, the larger CL and V may be attributed to the high BMI in the study population as the authors suggested 11 .…”

Section: Discussionmentioning

confidence: 98%

“…The PK of remdesivir in COVID‐19 is poorly understood despite the clinical need for remdesivir. Real‐world clinical studies have evaluated the PK of remdesivir and GS‐441524 in patients with COVID‐19 10–12,15,16 . A few real‐world PK studies on remdesivir, including two PopPK analyses, 11,12 have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…The PKs in patients with COVID‐19, including those with severe symptoms or renal impairment, was unknown at stating compassionate use 9 . Thereafter, real‐world studies in clinical practice have focused on remdesivir and GS‐441524 PKs in COVID‐19, including patients with end‐stage renal dysfunction 10–12 . However, the exposure–clinical outcome relationship in patients with COVID‐19 has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics and exposure–clinical outcome relationship of remdesivir major metabolite GS‐441524 in patients with moderate and severe COVID‐19

Tamura

Irie

Nakagawa

et al. 2023

CPT Pharmacom & Syst Pharma

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics and exposure–clinical outcome relationship of remdesivir major metabolite GS‐441524 in patients with moderate and severe COVID‐19

Tamura

Irie

Nakagawa

et al. 2023

CPT Pharmacom & Syst Pharma

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“…This might include currently available antivirals, such as molnupiravir or remdesivir ( 46 , 47 ), but other agents that have recently been approved in other settings such as ensitrelvir ( 48 ) or are under development, e.g. GS441525 ( 49 ), could also be considered. Ultimately, the route of administration, side effect profile, and drug-drug interactions will decide which antiviral, if efficacious, is optimal.…”

Section: Current State Of Long Covid Management and Potential Therape...mentioning

confidence: 99%

Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative

et al. 2023

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Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.

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Remdesivir: A Review in COVID-19

Blair

2023

Drugs

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Remdesivir (Veklury ® ), a nucleotide analogue prodrug with broad-spectrum antiviral activity, is approved for the treatment of coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 infection. Unlike some antivirals, remdesivir has a low potential for drug-drug interactions. In the pivotal ACTT-1 trial in hospitalized patients with COVID-19, daily intravenous infusions of remdesivir significantly reduced time to recovery relative to placebo. Subsequent trials provided additional support for the efficacy of remdesivir in hospitalized patients with moderate or severe COVID-19, with a greater benefit seen in patients with minimal oxygen requirements at baseline. Clinical trials also demonstrated the efficacy of remdesivir in other patient populations, including outpatients at high risk for progression to severe COVID-19, as well as hospitalized paediatric patients. In terms of mortality, results were equivocal. However, remdesivir appeared to have a small mortality benefit in hospitalized patients who were not already being ventilated at baseline. Remdesivir was generally well tolerated in clinical trials, but pharmacovigilance data found an increased risk of hepatic, renal and cardiovascular adverse drug reactions in the real-world setting. In conclusion, remdesivir represents a useful treatment option for patients with COVID-19, particularly those who require supplemental oxygen. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-023-01926-0.

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Population Pharmacokinetics of Remdesivir and GS-441524 in Hospitalized COVID-19 Patients

Cited by 15 publications

References 33 publications

Population pharmacokinetics and exposure–clinical outcome relationship of remdesivir major metabolite GS‐441524 in patients with moderate and severe COVID‐19

Population pharmacokinetics and exposure–clinical outcome relationship of remdesivir major metabolite GS‐441524 in patients with moderate and severe COVID‐19

Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative

Remdesivir: A Review in COVID-19

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