id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-253606-o8a0jhx2	Mégarbane, Bruno	Comment on: Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial	2020-08-07		.txt	text/plain	844	58	44	4 Thirdly, using in vitro anti-SARS-CoV-2 activity and drug exposure at the putative target site of action to determine the effective regimen in vivo is misleading. 4 Interestingly, one mechanistic PK/virological/QTc model developed to predict SARS-CoV-2 decline rate and QTc prolongation suggested that only elevated hydroxychloroquine regimens (>400 mg twice daily for 5 days) are predicted to rapidly decrease viral loads, reduce the infected patient proportion and shorten the treatment course, compared with routine regimens (400 mg daily). To conclude, prediction of the effective hydroxychloroquine regimen to treat the SARS-CoV-2-infected patient is doomed due to uncertainties related to the lack of in vitro model reliability and EC 50 pertinence and to the weakness of used PBPK models that did not mirror hydroxychloroquine PK complexity at the intracellular target level. Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial	./cache/cord-253606-o8a0jhx2.txt	./txt/cord-253606-o8a0jhx2.txt