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1/7 France has done the first pharmacokinetic (PK) study of HCQ for ICU patients of #COVID19, a fantastic job for dosage optimization.
13 patients, average weight=82.7 kg
46% pts BMI>30
12 on mechanical ventilators
1 on ECMO
30.7% with medium/severe renal dysfunction https://twitter.com/aknappjr/status/1248312523998121985
13 patients, average weight=82.7 kg46% pts BMI>3012 on mechanical ventilators 1 on ECMO30.7% with medium/severe renal dysfunction https://twitter.com/aknappjr/status/1248312523998121985
2/7
2 pts had QT prolongations (>500ms ), but not related to HCQ levels.
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 pts had QT prolongations (>500ms ), but not related to HCQ levels. 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
3/7
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.
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
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.
Regimen C: 800+600mg day1, then 600mg/day for 4 days, blood levels exceeds 2mg/L after 8 hrs
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.Regimen C: 800+600mg day1, then 600mg/day for 4 days, blood levels exceeds 2mg/L after 8 hrs
5/7
Another PBPK report also recommends a similar regimen; 400mg/day+loading dose
the lung concentration will reach level ~400 times higher than those in the blood.
if 400mg/day from day 2, the ratio of lung concentration/EC50 will reach 85.4 on day 5,
and 154 on day 10.
Another PBPK report also recommends a similar regimen; 400mg/day+loading dosethe lung concentration will reach level ~400 times higher than those in the blood.if 400mg/day from day 2, the ratio of lung concentration/EC50 will reach 85.4 on day 5, and 154 on day 10.
6/7
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
Dosage should be further individualized to WEIGHT, renal and heart condition, etc
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 Dosage should be further individualized to WEIGHT, renal and heart condition, etc
