Dosing ARBs for COVID-19

philipn authored on Nov. 16, 2020, 5:14 a.m.

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If ARBs (or other drugs modulating the renin-angiotensin system) help in COVID-19, what would be the ideal dosing and medication to use? This page explores this question. Dose & medication used in animal studies ACE2-knockout animal studies: 15 mg/kg losartan (route of administration unspecified) in mice. Result: attenuation of lung injury from SARS spike protein + acid combination. Note that this was an acute injury: the mice were challenged with acid once after losartan was given. Human equivalent dose (80kg human): 97 mg losartan. 50 mg/kg/day (route of administration unspecified) irbesartan in mice. Result: "rescued the systolic dysfunction, normalized altered signaling pathways, flow-mediated dilation, and the increased oxidative stress in the cardiovascular system." Human equivalent dose (80kg human): 324 mg irbesartan. Other animal studies of AT1R blockade: 30 mg/kg losartan, intravenous, in mice. Ang II and thrombosis. Result: "losartan abolished prothrombotic effect of Ang II" Human equivalent dose (80kg human): 195 mg losartan. But the mouse study used I.V. dosing, not oral. 30mg/kg losartan, p.o., in mice. Induced arterial thrombosis. Result: significantly attenuated thrombosis (42% versus control) Human equivalent dose (80kg human): 195 mg losartan. Dose & medication used in clinical trials Losartan: 12.5mg bid. 200 participants total. 25mg od for 14 days. Multi-arm trial, estimate ~1000 participants total. 25mg od for 10 days. 580 participants total. 25mg bid. 20 participants total. 25mg bid for 14 days. 100 participants total. 25 od, escaled to 50mg. 34 participants total. 50mg od. 200 participants total. 50mg od for 15 days. 176 participants total. 100mg od. Multi-arm trial, estimate ~5000 participants. Titration up to 100mg od over 3 days. 1372 participants total. Valsartan: Titrated based on BP, max 160mg bid. 651 participants total. Telmisartan: 20mg od. 338 participants total. 40mg od for 21 days. 40 participants total. 40mg od for 14 days. 60 participants total. 80mg bid. 400 participants total. Candesartan: 4mg od, "titrated to normotension". Multi-arm trial, estimated ~50 participants total. Unspecified ARB/dose: CLARITY trial. 605 participants total.	If ARBs (or other drugs modulating the renin-angiotensin system) help in COVID-19, what would be the ideal dosing and medication to use? This page explores this question. Dose & medication used in animal studies ACE2-knockout animal studies: 15 mg/kg losartan (route of administration unspecified) in mice. Result: attenuation of lung injury from SARS spike protein + acid combination. Note that this was an acute injury: the mice were challenged with acid once after losartan was given. Human equivalent dose (80kg human): 97 mg losartan. 50 mg/kg/day (route of administration unspecified) irbesartan in mice. Result: "rescued the systolic dysfunction, normalized altered signaling pathways, flow-mediated dilation, and the increased oxidative stress in the cardiovascular system." Human equivalent dose (80kg human): 324 mg irbesartan. Other animal studies of AT1R blockade: 30 mg/kg losartan, intravenous, in mice. Ang II and thrombosis. Result: "losartan abolished prothrombotic effect of Ang II" Human equivalent dose (80kg human): 195 mg losartan. But the mouse study used I.V. dosing, not oral. 30mg/kg losartan, p.o., in mice. Induced arterial thrombosis. Result: significantly attenuated thrombosis (42% versus control) Human equivalent dose (80kg human): 195 mg losartan. 10 mg/kg losartan, p.o., in mice. Induction of venous thrombosis. Result: significantly decreased thrombus weight. Human equivalent dose (80kg human): 65 mg losartan. 30 mg/kg losartan, in drinking water, in mice. ACE2 deficiency increases NADPH‐mediated oxidative stress. Result: normalization of NADPH oxidase activity in ACE2-knockout mice. Human equivalent dose (80kg human): 195 mg losartan. Dose & medication used in clinical trials Losartan: 12.5mg bid. 200 participants total. 25mg od for 14 days. Multi-arm trial, estimate ~1000 participants total. 25mg od for 10 days. 580 participants total. 25mg bid. 20 participants total. 25mg bid for 14 days. 100 participants total. 25 od, escaled to 50mg. 34 participants total. 50mg od. 200 participants total. 50mg od for 15 days. 176 participants total. 100mg od. Multi-arm trial, estimate ~5000 participants. Titration up to 100mg od over 3 days. 1372 participants total. Valsartan: Titrated based on BP, max 160mg bid. 651 participants total. Telmisartan: 20mg od. 338 participants total. 40mg od for 21 days. 40 participants total. 40mg od for 14 days. 60 participants total. 80mg bid. 400 participants total. Candesartan: 4mg od, "titrated to normotension". Multi-arm trial, estimated ~50 participants total. Unspecified ARB/dose: CLARITY trial. 605 participants total.

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If ARBs (or other drugs modulating the renin-angiotensin system) help in COVID-19, what would be the ideal dosing and medication to use? This page explores this question.

Dose & medication used in animal studies

ACE2-knockout animal studies:

15 mg/kg losartan (route of administration unspecified) in mice. Result: attenuation of lung injury from SARS spike protein + acid combination. Note that this was an acute injury: the mice were challenged with acid once after losartan was given.
- Human equivalent dose (80kg human): 97 mg losartan.
50 mg/kg/day (route of administration unspecified) irbesartan in mice. Result: "rescued the systolic dysfunction, normalized altered signaling pathways, flow-mediated dilation, and the increased oxidative stress in the cardiovascular system."
- Human equivalent dose (80kg human): 324 mg irbesartan.

Other animal studies of AT1R blockade:

30 mg/kg losartan, intravenous, in mice. Ang II and thrombosis. Result: "losartan abolished prothrombotic effect of Ang II"
- Human equivalent dose (80kg human): 195 mg losartan. But the mouse study used I.V. dosing, not oral.
30mg/kg losartan, p.o., in mice. Induced arterial thrombosis. Result: significantly attenuated thrombosis (42% versus control)
- Human equivalent dose (80kg human): 195 mg losartan.

Dose & medication used in clinical trials

If ARBs (or other drugs modulating the renin-angiotensin system) help in COVID-19, what would be the ideal dosing and medication to use? This page explores this question.

Dose & medication used in animal studies

ACE2-knockout animal studies:

15 mg/kg losartan (route of administration unspecified) in mice. Result: attenuation of lung injury from SARS spike protein + acid combination. Note that this was an acute injury: the mice were challenged with acid once after losartan was given.
- Human equivalent dose (80kg human): 97 mg losartan.
50 mg/kg/day (route of administration unspecified) irbesartan in mice. Result: "rescued the systolic dysfunction, normalized altered signaling pathways, flow-mediated dilation, and the increased oxidative stress in the cardiovascular system."
- Human equivalent dose (80kg human): 324 mg irbesartan.

Other animal studies of AT1R blockade:

30 mg/kg losartan, intravenous, in mice. Ang II and thrombosis. Result: "losartan abolished prothrombotic effect of Ang II"
- Human equivalent dose (80kg human): 195 mg losartan. But the mouse study used I.V. dosing, not oral.
30mg/kg losartan, p.o., in mice. Induced arterial thrombosis. Result: significantly attenuated thrombosis (42% versus control)
- Human equivalent dose (80kg human): 195 mg losartan.
10 mg/kg losartan, p.o., in mice. Induction of venous thrombosis. Result: significantly decreased thrombus weight.
- Human equivalent dose (80kg human): 65 mg losartan.
30 mg/kg losartan, in drinking water, in mice. ACE2 deficiency increases NADPH‐mediated oxidative stress. Result: normalization of NADPH oxidase activity in ACE2-knockout mice.
- Human equivalent dose (80kg human): 195 mg losartan.

philipn / Dosing ARBs for COVID-19 39ea3a0bc39063fcf9014a97c1a40c3d382e6bcc

Dose & medication used in animal studies

Dose & medication used in clinical trials

Dose & medication used in animal studies

Dose & medication used in clinical trials