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PMC:7696151 / 39262-41349 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
1147 640-650 Species denotes SARS-CoV-2 Tax:2697049
1148 1204-1212 Species denotes patients Tax:9606
1149 1892-1902 Species denotes SARS-CoV-2 Tax:2697049
1150 17-20 Chemical denotes HCQ MESH:D006886
1151 225-228 Chemical denotes HCQ MESH:D006886
1152 370-373 Chemical denotes HCQ MESH:D006886
1153 514-517 Chemical denotes HCQ MESH:D006886
1154 632-635 Chemical denotes HCQ MESH:D006886
1155 721-724 Chemical denotes HCQ MESH:D006886
1156 865-868 Chemical denotes HCQ MESH:D006886
1157 1723-1726 Chemical denotes HCQ MESH:D006886
1158 1863-1866 Chemical denotes HCQ MESH:D006886
1159 34-54 Disease denotes SARS-CoV-2 infection MESH:C000657245
1160 334-354 Disease denotes SARS-CoV-2 infection MESH:C000657245
1161 1195-1203 Disease denotes COVID-19 MESH:C000657245
1162 1508-1523 Disease denotes Garcia-Cremades MESH:C536767
1163 2071-2086 Disease denotes QT prolongation MESH:D008133

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T256 0-90 Sentence denotes To conclude, the HCQ treatment of SARS-CoV-2 infection was not met with its hoped success.
T257 91-248 Sentence denotes This is probably related to the inability of the dosing regimens currently in use to achieve the blood concentration required for the HCQ antiviral activity.
T258 249-487 Sentence denotes Initially, based on physiological pharmacokinetic models, Yao et al. recommended for SARS-CoV-2 infection a loading oral HCQ dose of 400 mg twice daily, followed by a maintenance dose of 200 mg administered twice daily for four days [50].
T259 488-825 Sentence denotes However, this recommended HCQ dosage regimen was based only on the ratio of free lung trough concentration to in vitro EC50 values (the EC50 of HCQ for SARS-CoV-2 ranged between 0.72 and 17.31µM) and did not consider the tendency of HCQ to accumulate within acidic cellular organelles like endosomes, lysosomes, and Golgi apparatus [69].
T260 826-981 Sentence denotes In fact, it has been demonstrated that HCQ concentration in lysosomes is higher than the extracellular concentration (80 µM vs. 0.5 µM, respectively) [70].
T261 982-1145 Sentence denotes Based on these results, it was considered necessary to compare the EC50 values obtained in vitro with the plasma concentration and not with the lung concentration.
T262 1146-1434 Sentence denotes In a study investigating HCQ pharmacokinetics in COVID-19 patients treated with 600 mg/day of HCQ, it was found that the mean blood concentration of HCQ was 0.46 mg/day [32], which was below the lowest estimated levels of 0.48 mg/mL corresponding to the in vitro concentration of 0.72 µM.
T263 1435-1642 Sentence denotes Further, a plasma concentration predicted for HCQ antiviral EC50 made by Garcia-Cremades et al. found that it should be 4,7 µM corresponding to 1.58 mg/mL, which is much higher than in vivo plasmatic values.
T264 1643-1833 Sentence denotes To reach this plasma concentration, it should be necessary to take an amount of HCQ higher than 400 mg twice a day for five days or more [71], which would increase the onset of side effects.
T265 1834-2087 Sentence denotes Thus, the ineffectiveness of HCQ antiviral activity again SARS-CoV-2 can be related to the low current dosing regimens and the impossibility to increase the administered doses due to the increased risk of severe side effects, especially QT prolongation.