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Mol Pharm ; 20(1): 750-757, 2023 01 02.
Article in English | MEDLINE | ID: mdl-36448927

ABSTRACT

Vaccine hesitancy and the occurrence of elusive variants necessitate further treatment options for coronavirus disease 2019 (COVID-19). Accumulated evidence indicates that clinically used hypertensive drugs, angiotensin receptor blockers (ARBs), may benefit patients by mitigating disease severity and/or viral propagation. However, current clinical formulations administered orally pose systemic safety concerns and likely require a very high dose to achieve the desired therapeutic window in the lung. To address these limitations, we have developed a nanosuspension formulation of an ARB, entirely based on clinically approved materials, for inhaled treatment of COVID-19. We confirmed in vitro that our formulation exhibits physiological stability, inherent drug activity, and inhibitory effect against SARV-CoV-2 replication. Our formulation also demonstrates excellent lung pharmacokinetics and acceptable tolerability in rodents and/or nonhuman primates following direct administration into the lung. Thus, we are currently pursuing clinical development of our formulation for its uses in patients with COVID-19 or other respiratory infections.


Subject(s)
COVID-19 , Respiratory Tract Infections , Animals , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Telmisartan , Renin-Angiotensin System/physiology , SARS-CoV-2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Respiratory Tract Infections/drug therapy
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