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

Tamura, Ryo; Irie, Kei; Nakagawa, Atsushi; Muroi, Hirohito; Eto, Masashi; Ikesue, Hiroaki; Muroi, Nobuyuki; Fukushima, Shoji; Tomii, Keisuke; Hashida, Tohru

doi:10.1002/psp4.12936

Cited by 4 publications

(2 citation statements)

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“…The median terminal half-lives of remdesivir and GS-441524 were ≈ 1 h and ≈ 27 h, respectively [ 6 , 7 ]. In population pharmacokinetic analyses of hospitalized patients with COVID-19, remdesivir was eliminated rapidly, while GS-441524 was eliminated relatively slowly [ 18 , 19 ].…”

Section: Pharmacokinetic Properties Of Remdesivirmentioning

confidence: 99%

“…Kidney function and the timing of remdesivir administration around dialysis had no effect on the pharmacokinetics of remdesivir [ 6 , 7 ]. The clearance of GS-441524 is dependent on the estimated glomerular filtration rate (eGFR) [ 18 , 19 , 21 ]. Although exposures of GS-441524 and GS-704277 were increased in patients with renal impairment relative to those with normal renal function, this finding was not clinically significant [ 6 , 7 ].…”

Section: Pharmacokinetic Properties Of Remdesivirmentioning

confidence: 99%

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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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Section: Pharmacokinetic Properties Of Remdesivirmentioning

confidence: 99%