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10.1002/cpt.1909 http://scihub22266oqcxt.onion/10.1002/cpt.1909 C7280633!7280633 !32438446     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 294.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 294.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\32438446 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Clin+Pharmacol+Ther 2020 ; 108 (4 ): 775-790 Nephropedia Template TP {{tp|p=32438446 |t=2020. Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics |pdf=|usr=}}{{32438446 }} gab.com Text Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics JO: Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32438446 #FOAvip There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC(90) ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (C(max) ) at an approved dose in humans (C(max) /EC(90) ratio). Only 14 of the 56 analyzed drugs achieved a C(max) /EC(90) ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (K(p) U(lung) ) was also simulated to derive a lung C(max) /half-maximal effective concentration (EC(50) ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC(50) . Nitazoxanide and sulfadoxine also exceeded their reported EC(50) by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC(90) values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials. Twit Text FOAVip Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics ????Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32438446 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32438446 #FOAvip English Wikipedia <ref>{{Cite pmid|32438446 }}</ref> Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics #MMPMID32438446 Arshad U ; Pertinez H ; Box H ; Tatham L ; Rajoli RKR ; Curley P ; Neary M ; Sharp J ; Liptrott NJ ; Valentijn A ; David C ; Rannard SP ; O'Neill PM ; Aljayyoussi G ; Pennington SH ; Ward SA ; Hill A ; Back DJ ; Khoo SH ; Bray PG ; Biagini GA ; Owen A Clin Pharmacol Ther 2020[Oct]; 108 (4 ): 775-790 PMID32438446 show ga There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC(90) ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (C(max) ) at an approved dose in humans (C(max) /EC(90) ratio). Only 14 of the 56 analyzed drugs achieved a C(max) /EC(90) ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (K(p) U(lung) ) was also simulated to derive a lung C(max) /half-maximal effective concentration (EC(50) ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC(50) . Nitazoxanide and sulfadoxine also exceeded their reported EC(50) by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC(90) values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials. |Antiviral Agents/*administration & dosage/blood [MESH] |Betacoronavirus/*drug effects [MESH] |COVID-19 [MESH] |Coronavirus Infections/blood/*drug therapy [MESH] |Drug Delivery Systems/*methods [MESH] |Drug Repositioning/*methods [MESH] |Humans [MESH] |Pandemics [MESH] |Pneumonia, Viral/blood/*drug therapy [MESH]Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based(epmc).pdf DeepDyve Pubget Overpricing