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10.1002/cpt.2014 http://scihub22266oqcxt.onion/10.1002/cpt.2014 32767755!7436510!32767755     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Pharmacol+Ther 2020 ; 108 (6): 1176-1184 Nephropedia Template TP {{tp|p=32767755|t=2020. Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS-CoV-2 |pdf=|usr=}}{{32767755}} gab.com Text Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS-CoV-2 JO: Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32767755 #FOAvip Lopinavir/ritonavir, originally developed for treating HIV, is currently undergoing clinical studies for treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although recent reports suggest that lopinavir exhibits in vitro efficacy against SARS-CoV-2, it is a highly protein-bound drug and it remains unknown if it reaches adequate in vivo unbound (free) concentrations in lung tissue. We built a physiologically-based pharmacokinetic model of lopinavir/ritonavir in white and Chinese populations. Our aim was to perform pharmacokinetic/pharmacodynamic correlations by comparing simulated free plasma and lung concentration values achieved using different dosing regimens of lopinavir/ritonavir with unbound half-maximal effective concentration (EC(50,unbound) ) and unbound effective concentration 90% values of lopinavir against SARS-CoV-2. The model was validated against multiple observed clinical datasets for single and repeated dosing of lopinavir/ritonavir. Predicted pharmacokinetic parameters, such as the maximum plasma concentration, area under the plasma concentration-time profile, oral clearance, half-life, and minimum plasma concentration at steady-state were within two-fold of clinical values for both populations. Using the current lopinavir/ritonavir regimen of 400/100 mg twice daily, lopinavir does not achieve sufficient free lung concentrations for efficacy against SARS-CoV-2. Although the Chinese population reaches greater plasma and lung concentrations as compared with whites, our simulations suggest that a significant dose increase from the current clinically used dosing regimen is necessary to reach the EC(50,unbound) value for both populations. Based on safety data, higher doses would likely lead to QT prolongation and gastrointestinal disorders (nausea, vomiting, and diarrhea), thus, any dose adjustment must be carefully weighed alongside these safety concerns. Twit Text FOAVip Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS-CoV-2 ????Clin Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=32767755 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32767755 #FOAvip English Wikipedia <ref>{{Cite pmid|32767755}}</ref> Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS-CoV-2 #MMPMID32767755 Thakur A; Tan SPF; Chan JCY Clin Pharmacol Ther 2020[Dec]; 108 (6): 1176-1184 PMID32767755show ga Lopinavir/ritonavir, originally developed for treating HIV, is currently undergoing clinical studies for treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although recent reports suggest that lopinavir exhibits in vitro efficacy against SARS-CoV-2, it is a highly protein-bound drug and it remains unknown if it reaches adequate in vivo unbound (free) concentrations in lung tissue. We built a physiologically-based pharmacokinetic model of lopinavir/ritonavir in white and Chinese populations. Our aim was to perform pharmacokinetic/pharmacodynamic correlations by comparing simulated free plasma and lung concentration values achieved using different dosing regimens of lopinavir/ritonavir with unbound half-maximal effective concentration (EC(50,unbound) ) and unbound effective concentration 90% values of lopinavir against SARS-CoV-2. The model was validated against multiple observed clinical datasets for single and repeated dosing of lopinavir/ritonavir. Predicted pharmacokinetic parameters, such as the maximum plasma concentration, area under the plasma concentration-time profile, oral clearance, half-life, and minimum plasma concentration at steady-state were within two-fold of clinical values for both populations. Using the current lopinavir/ritonavir regimen of 400/100 mg twice daily, lopinavir does not achieve sufficient free lung concentrations for efficacy against SARS-CoV-2. Although the Chinese population reaches greater plasma and lung concentrations as compared with whites, our simulations suggest that a significant dose increase from the current clinically used dosing regimen is necessary to reach the EC(50,unbound) value for both populations. Based on safety data, higher doses would likely lead to QT prolongation and gastrointestinal disorders (nausea, vomiting, and diarrhea), thus, any dose adjustment must be carefully weighed alongside these safety concerns. |*COVID-19 Drug Treatment[MESH] |Antiviral Agents/*pharmacokinetics[MESH] |Area Under Curve[MESH] |Asian People[MESH] |Dose-Response Relationship, Drug[MESH] |HIV Infections/drug therapy[MESH] |Half-Life[MESH] |Humans[MESH] |Lopinavir/*pharmacokinetics/pharmacology[MESH] |Lung/metabolism[MESH] |Metabolic Clearance Rate[MESH] |Models, Biological[MESH] |Ritonavir/*pharmacokinetics/pharmacology[MESH] |SARS-CoV-2[MESH]Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical(epmc).pdf DeepDyve Pubget Overpricing