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10.1002/cpt.1856 http://scihub22266oqcxt.onion/10.1002/cpt.1856 32285930!7262072!32285930     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Pharmacol+Ther 2020 ; 108 (2): 253-263 Nephropedia Template TP {{tp|p=32285930|t=2020. Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing |pdf=|usr=}}{{32285930}} gab.com Text Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing JO: Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32285930 #FOAvip Hydroxychloroquine (HCQ) is a promising candidate for Coronavirus disease of 2019 (COVID-19) treatment. The optimal dosing of HCQ is unknown. Our goal was to integrate historic and emerging pharmacological and toxicity data to understand safe and efficacious HCQ dosing strategies for COVID-19 treatment. The data sources included were (i) longitudinal clinical, pharmacokinetic (PK), and virologic data from patients with severe acute respiratory syndrome-2 (SARS-CoV-2) infection who received HCQ with or without azithromycin (n = 116), (ii) in vitro viral replication data and SARS-CoV-2 viral load inhibition by HCQ, (iii) a population PK model of HCQ, and (iv) a model relating chloroquine PKs to corrected QT (QTc) prolongation. A mechanistic PK/virologic/QTc model for HCQ was developed and externally validated to predict SARS-CoV-2 rate of viral decline and QTc prolongation. SARS-CoV-2 viral decline was associated with HCQ PKs (P < 0.001). The extrapolated patient half-maximal effective concentration (EC(50) ) was 4.7 microM, comparable to the reported in vitro EC(50s) . HCQ doses > 400 mg b.i.d. for >/=5 days were predicted to rapidly decrease viral loads, reduce the proportion of patients with detectable SARS-CoV-2 infection, and shorten treatment courses, compared with lower dose (</= 400 mg daily) regimens. However, HCQ doses > 600 mg b.i.d. were also predicted to prolong QTc intervals. This prolongation may have clinical implications warranting further safety assessment. Due to COVID-19's variable natural history, lower dose HCQ regimens may be indistinguishable from controls. Evaluation of higher HCQ doses is needed to ensure adequate safety and efficacy. Twit Text FOAVip Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing ????Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32285930 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32285930 #FOAvip English Wikipedia <ref>{{Cite pmid|32285930}}</ref> Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing #MMPMID32285930 Garcia-Cremades M; Solans BP; Hughes E; Ernest JP; Wallender E; Aweeka F; Luetkemeyer AF; Savic RM Clin Pharmacol Ther 2020[Aug]; 108 (2): 253-263 PMID32285930show ga Hydroxychloroquine (HCQ) is a promising candidate for Coronavirus disease of 2019 (COVID-19) treatment. The optimal dosing of HCQ is unknown. Our goal was to integrate historic and emerging pharmacological and toxicity data to understand safe and efficacious HCQ dosing strategies for COVID-19 treatment. The data sources included were (i) longitudinal clinical, pharmacokinetic (PK), and virologic data from patients with severe acute respiratory syndrome-2 (SARS-CoV-2) infection who received HCQ with or without azithromycin (n = 116), (ii) in vitro viral replication data and SARS-CoV-2 viral load inhibition by HCQ, (iii) a population PK model of HCQ, and (iv) a model relating chloroquine PKs to corrected QT (QTc) prolongation. A mechanistic PK/virologic/QTc model for HCQ was developed and externally validated to predict SARS-CoV-2 rate of viral decline and QTc prolongation. SARS-CoV-2 viral decline was associated with HCQ PKs (P < 0.001). The extrapolated patient half-maximal effective concentration (EC(50) ) was 4.7 microM, comparable to the reported in vitro EC(50s) . HCQ doses > 400 mg b.i.d. for >/=5 days were predicted to rapidly decrease viral loads, reduce the proportion of patients with detectable SARS-CoV-2 infection, and shorten treatment courses, compared with lower dose ( 600 mg b.i.d. were also predicted to prolong QTc intervals. This prolongation may have clinical implications warranting further safety assessment. Due to COVID-19's variable natural history, lower dose HCQ regimens may be indistinguishable from controls. Evaluation of higher HCQ doses is needed to ensure adequate safety and efficacy. |Antiviral Agents/administration & dosage/pharmacokinetics[MESH] |Betacoronavirus/*drug effects/physiology[MESH] |COVID-19 Drug Treatment[MESH] |Coronavirus Infections/drug therapy/virology[MESH] |Drug Repositioning[MESH] |Humans[MESH] |Hydroxychloroquine/*administration & dosage/*pharmacokinetics[MESH] |Models, Biological[MESH] |Reproducibility of Results[MESH] |SARS-CoV-2[MESH] |Severe acute respiratory syndrome-related coronavirus/drug effects/physiology[MESH] |Translational Research, Biomedical[MESH] |Viral Load/drug effects[MESH]Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An In(epmc).pdf DeepDyve Pubget Overpricing