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10.1111/cts.12975 http://scihub22266oqcxt.onion/10.1111/cts.12975 33404204!8212743!33404204     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Transl+Sci 2021 ; 14 (3): 1082-1091 Nephropedia Template TP {{tp|p=33404204|t=2021. Hybrid physiologically-based pharmacokinetic model for remdesivir: Application to SARS-CoV-2 |pdf=|usr=}}{{33404204}} gab.com Text Hybrid physiologically-based pharmacokinetic model for remdesivir: Application to SARS-CoV-2 JO: Clin Transl Sci http://www.kidney.de/pget.php?&tw=1&pmid=33404204 #FOAvip A novel coronavirus, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), has caused a pandemic that continues to cause catastrophic health and economic carnage and has escalated the identification and development of antiviral agents. Remdesivir (RDV), a prodrug and requires intracellular conversions to the active triphosphate nucleoside (TN) has surfaced as an active anti-SARS-CoV-2 drug. To properly design therapeutic treatment regimens, it is imperative to determine if adequate intracellular TN concentrations are achieved in target tissues, such as the lungs. Because measurement of such concentrations is unrealistic in patients, a physiologically-based pharmacokinetic (PBPK) model was developed to characterize RDV and TN disposition. Specifically, a hybrid PBPK model was developed based on previously reported data in humans. The model represented each tissue as a two-compartment model-both extracellular and intracellular compartment wherein each intracellular compartment contained a comprehensive metabolic model to the ultimate active metabolite TN. Global sensitivity analyses and Monte-Carlo simulations were conducted to assess which parameters and how highly sensitive ones impacted peripheral blood mononuclear cells and intracellular lung TN profiles. Finally, clinical multiple-dose regimens indicated that minimum lung intracellular TN concentrations ranged from ~ 9 uM to 4 uM, which suggest current regimens are effective based on in vitro half-maximal effective concentration values. The model can be used to explore tissue drug disposition under various conditions and regimens, and expanded to pharmacodynamic models. Twit Text FOAVip Hybrid physiologically-based pharmacokinetic model for remdesivir: Application to SARS-CoV-2 ????Clin Transl Sci http://www.kidney.de/pget.php?&tw=1&pmid=33404204 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33404204 #FOAvip English Wikipedia <ref>{{Cite pmid|33404204}}</ref> Hybrid physiologically-based pharmacokinetic model for remdesivir: Application to SARS-CoV-2 #MMPMID33404204 Gallo JM Clin Transl Sci 2021[May]; 14 (3): 1082-1091 PMID33404204show ga A novel coronavirus, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), has caused a pandemic that continues to cause catastrophic health and economic carnage and has escalated the identification and development of antiviral agents. Remdesivir (RDV), a prodrug and requires intracellular conversions to the active triphosphate nucleoside (TN) has surfaced as an active anti-SARS-CoV-2 drug. To properly design therapeutic treatment regimens, it is imperative to determine if adequate intracellular TN concentrations are achieved in target tissues, such as the lungs. Because measurement of such concentrations is unrealistic in patients, a physiologically-based pharmacokinetic (PBPK) model was developed to characterize RDV and TN disposition. Specifically, a hybrid PBPK model was developed based on previously reported data in humans. The model represented each tissue as a two-compartment model-both extracellular and intracellular compartment wherein each intracellular compartment contained a comprehensive metabolic model to the ultimate active metabolite TN. Global sensitivity analyses and Monte-Carlo simulations were conducted to assess which parameters and how highly sensitive ones impacted peripheral blood mononuclear cells and intracellular lung TN profiles. Finally, clinical multiple-dose regimens indicated that minimum lung intracellular TN concentrations ranged from ~ 9 uM to 4 uM, which suggest current regimens are effective based on in vitro half-maximal effective concentration values. The model can be used to explore tissue drug disposition under various conditions and regimens, and expanded to pharmacodynamic models. |*COVID-19 Drug Treatment[MESH] |*SARS-CoV-2[MESH] |Adenosine Monophosphate/administration & dosage/*analogs & derivatives/pharmacokinetics/therapeutic use[MESH] |Alanine/administration & dosage/*analogs & derivatives/pharmacokinetics/therapeutic use[MESH] |Antiviral Agents/*pharmacokinetics[MESH] |Humans[MESH]Hybrid physiologically-based pharmacokinetic model for remdesivir: App(epmc).pdf DeepDyve Pubget Overpricing