Thread by @88549439, 1/7 France has done the first pharmacokinetic (PK) study of HCQ for [...]

1/7 France has done the first pharmacokinetic (PK) study of HCQ for ICU patients of #COVID19, a fantastic job for dosage optimization.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">13 patients, average weight=82.7 kg

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">46% pts BMI>30

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">12 on mechanical ventilators

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">1 on ECMO

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">30.7% with medium/severe renal dysfunction https://twitter.com/aknappjr/status/1248312523998121985">https://twitter.com/aknappjr/...

https://twitter.com/aknappjr/status/1248312523998121985

2/7

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">2 pts had QT prolongations (>500ms ), but not related to HCQ levels.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond"> Regimen D: 200mgX3/day for 7 days;
PK simulation shows HCQ reached the therapeutic level of 1mg/L on day 2.5 but exceeds 2mg/L (risk of ocular toxicity) on day 5

2/7https://abs.twimg.com/emoji/v2/... draggable=

2 pts had QT prolongations (>500ms ), but not related to HCQ levels.https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond"> Regimen D: 200mgX3/day for 7 days;PK simulation shows HCQ reached the therapeutic level of 1mg/L on day 2.5 but exceeds 2mg/L (risk of ocular toxicity) on day 5" title="2/7https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">2 pts had QT prolongations (>500ms ), but not related to HCQ levels.https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond"> Regimen D: 200mgX3/day for 7 days;PK simulation shows HCQ reached the therapeutic level of 1mg/L on day 2.5 but exceeds 2mg/L (risk of ocular toxicity) on day 5" class="img-responsive" style="max-width:100%;"/>

3/7

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔺" title="Up-pointing red triangle" aria-label="Emoji: Up-pointing red triangle">In this D regimen, the average HCQ dose is ~7.5 mg/kg/day, which is above the well established safe upper limit: 6.5 mg/kg/day; meanwhile, the HCQ blood concentration exceeds the upper safe level: 2mg/L.

4/7

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">Regimen E: 800mg loading dose, 1mg/L can be reached on day 1, then 400mg (~5mg/kg/day) daily for 6 days, blood levels can be maintained in the therapeutic window for 7 days.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">Regimen C: 800+600mg day1, then 600mg/day for 4 days, blood levels exceeds 2mg/L after 8 hrs

4/7https://abs.twimg.com/emoji/v2/... draggable=

Regimen E: 800mg loading dose, 1mg/L can be reached on day 1, then 400mg (~5mg/kg/day) daily for 6 days, blood levels can be maintained in the therapeutic window for 7 days.https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">Regimen C: 800+600mg day1, then 600mg/day for 4 days, blood levels exceeds 2mg/L after 8 hrs" title="4/7https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">Regimen E: 800mg loading dose, 1mg/L can be reached on day 1, then 400mg (~5mg/kg/day) daily for 6 days, blood levels can be maintained in the therapeutic window for 7 days.https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">Regimen C: 800+600mg day1, then 600mg/day for 4 days, blood levels exceeds 2mg/L after 8 hrs" class="img-responsive" style="max-width:100%;"/>

5/7

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">Another PBPK report also recommends a similar regimen; 400mg/day+loading dose

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">the lung concentration will reach level ~400 times higher than those in the blood.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">if 400mg/day from day 2, the ratio of lung concentration/EC50 will reach 85.4 on day 5,
and 154 on day 10.

5/7https://abs.twimg.com/emoji/v2/... draggable=

6/7

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond">In conclusion, considering efficacy and safety, 800mg Qd as a loading dose on 1st day, then 400mg/day Qd for 4-6 days is the optimal dosage regimen for HCQ to treat #COVID2019

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔸" title="Small orange diamond" aria-label="Emoji: Small orange diamond"> Dosage should be further individualized to WEIGHT, renal and heart condition, etc

7/7 the second paper link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108130/
https://www.ncbi.nlm.nih.gov/pmc/artic... href="https://twtext.com//hashtag/SARSCoV2"> #SARSCoV2 #COVID2019 #medtwitter #covid4MDs #CriticalCare #hydrochloroquine
@InceptionCap @__ice9 @JamesTodaroMD @niro60487270

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the...

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108130/

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