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10.1007/s40262-021-00984-5 http://scihub22266oqcxt.onion/10.1007/s40262-021-00984-5 33782830!8007387!33782830     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33782830&cmd=llinks): Failed to open stream: HTTP request failed! 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Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor |pdf=|usr=}}{{33782830}} gab.com Text Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor JO: Clin Pharmacokinet http://www.kidney.de/pget.php?&tw=1&pmid=33782830 #FOAvip Remdesivir (RDV, Veklury((R))) is a once-daily, nucleoside ribonucleic acid polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 replication. Remdesivir has been granted approvals in several countries for use in adults and children hospitalized with severe coronavirus disease 2019 (COVID-19). Inside the cell, remdesivir undergoes metabolic activation to form the intracellular active triphosphate metabolite, GS-443902 (detected in peripheral blood mononuclear cells), and ultimately, the renally eliminated plasma metabolite GS-441524. This review discusses the pre-clinical pharmacology of RDV, clinical pharmacokinetics, pharmacodynamics/concentration-QT analysis, rationale for dose selection for treatment of patients with COVID-19, and drug-drug interaction potential based on available in vitro and clinical data in healthy volunteers. Following single-dose intravenous administration over 2 h of an RDV solution formulation across the dose range of 3-225 mg in healthy participants, RDV and its metabolites (GS-704277and GS-441524) exhibit linear pharmacokinetics. Following multiple doses of RDV 150 mg once daily for 7 or 14 days, major metabolite GS-441524 accumulates approximately 1.9-fold in plasma. Based on pharmacokinetic bridging from animal data and available human data in healthy volunteers, the RDV clinical dose regimen of a 200-mg loading dose on day 1 followed by 100-mg maintenance doses for 4 or 9 days was selected for further evaluation of pharmacokinetics and safety. Results showed high intracellular concentrations of GS-443902 suggestive of efficient conversion from RDV into the triphosphate form, and further supporting this clinical dosing regimen for the treatment of COVID-19. Mathematical drug-drug interaction liability predictions, based on in vitro and phase I data, suggest RDV has low potential for drug-drug interactions, as the impact of inducers or inhibitors on RDV disposition is minimized by the parenteral route of administration and extensive extraction. Using physiologically based pharmacokinetic modeling, RDV is not predicted to be a clinically significant inhibitor of drug-metabolizing enzymes or transporters in patients infected with COVID-19 at therapeutic RDV doses. Twit Text FOAVip Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor ????Clin Pharmacokinet http://www.kidney.de/pget.php?&tw=1&pmid=33782830 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33782830 #FOAvip English Wikipedia <ref>{{Cite pmid|33782830}}</ref> Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor #MMPMID33782830 Humeniuk R; Mathias A; Kirby BJ; Lutz JD; Cao H; Osinusi A; Babusis D; Porter D; Wei X; Ling J; Reddy YS; German P Clin Pharmacokinet 2021[May]; 60 (5): 569-583 PMID33782830show ga Remdesivir (RDV, Veklury((R))) is a once-daily, nucleoside ribonucleic acid polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 replication. Remdesivir has been granted approvals in several countries for use in adults and children hospitalized with severe coronavirus disease 2019 (COVID-19). Inside the cell, remdesivir undergoes metabolic activation to form the intracellular active triphosphate metabolite, GS-443902 (detected in peripheral blood mononuclear cells), and ultimately, the renally eliminated plasma metabolite GS-441524. This review discusses the pre-clinical pharmacology of RDV, clinical pharmacokinetics, pharmacodynamics/concentration-QT analysis, rationale for dose selection for treatment of patients with COVID-19, and drug-drug interaction potential based on available in vitro and clinical data in healthy volunteers. Following single-dose intravenous administration over 2 h of an RDV solution formulation across the dose range of 3-225 mg in healthy participants, RDV and its metabolites (GS-704277and GS-441524) exhibit linear pharmacokinetics. Following multiple doses of RDV 150 mg once daily for 7 or 14 days, major metabolite GS-441524 accumulates approximately 1.9-fold in plasma. Based on pharmacokinetic bridging from animal data and available human data in healthy volunteers, the RDV clinical dose regimen of a 200-mg loading dose on day 1 followed by 100-mg maintenance doses for 4 or 9 days was selected for further evaluation of pharmacokinetics and safety. Results showed high intracellular concentrations of GS-443902 suggestive of efficient conversion from RDV into the triphosphate form, and further supporting this clinical dosing regimen for the treatment of COVID-19. Mathematical drug-drug interaction liability predictions, based on in vitro and phase I data, suggest RDV has low potential for drug-drug interactions, as the impact of inducers or inhibitors on RDV disposition is minimized by the parenteral route of administration and extensive extraction. Using physiologically based pharmacokinetic modeling, RDV is not predicted to be a clinically significant inhibitor of drug-metabolizing enzymes or transporters in patients infected with COVID-19 at therapeutic RDV doses. |*COVID-19 Drug Treatment[MESH] |Adenosine Monophosphate/*analogs & derivatives/pharmacokinetics/pharmacology/therapeutic use[MESH] |Adenosine/analogs & derivatives[MESH] |Adult[MESH] |Alanine/*analogs & derivatives/pharmacokinetics/pharmacology/therapeutic use[MESH] |Animals[MESH] |Antiviral Agents/pharmacokinetics/*pharmacology[MESH] |Area Under Curve[MESH] |Dose-Response Relationship, Drug[MESH] |Drug Interactions[MESH] |Furans/metabolism[MESH] |Half-Life[MESH] |Humans[MESH] |Metabolic Clearance Rate[MESH] |Pyrroles/metabolism[MESH] |SARS-CoV-2[MESH]Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remd(epmc).pdf DeepDyve Pubget Overpricing