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10.1002/psp4.12685

http://scihub22266oqcxt.onion/10.1002/psp4.12685
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34292670!8420316!34292670
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suck abstract from ncbi


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pmid34292670      CPT+Pharmacometrics+Syst+Pharmacol 2021 ; 10 (10): 1161-1170
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  • Population pharmacokinetics of favipiravir in patients with COVID-19 #MMPMID34292670
  • Irie K; Nakagawa A; Fujita H; Tamura R; Eto M; Ikesue H; Muroi N; Fukushima S; Tomii K; Hashida T
  • CPT Pharmacometrics Syst Pharmacol 2021[Oct]; 10 (10): 1161-1170 PMID34292670show ga
  • The antiretroviral drug favipiravir (FPV) inhibits RNA-dependent RNA polymerase. It has been developed for the treatment of the novel coronavirus (severe acute respiratory syndrome coronavirus 2) infection disease, coronavirus disease 2019 (COVID-19). However, its pharmacokinetics in patients with COVID-19 is poorly understood. In this study, we measured FPV serum concentration by liquid chromatography-tandem mass spectrometry and conducted population pharmacokinetic analysis. A total of 39 patients were enrolled in the study: 33 were administered FPV 1600 mg twice daily (b.i.d.) on the first day followed by 600 mg b.i.d., and 6 were administered FPV 1800 mg b.i.d. on the first day followed by 800 mg or 600 mg b.i.d. The median age was 68 years (range, 27-89 years), 31 (79.5%) patients were men, median body surface area (BSA) was 1.72 m(2) (range, 1.11-2.2 m(2) ), and 10 (25.6%) patients required invasive mechanical ventilation (IMV) at the start of FPV. A total of 204 serum concentrations were available for pharmacokinetic analysis. A one-compartment model with first-order elimination was used to describe the pharmacokinetics. The estimated mean clearance/bioavailability (CL/F) and distribution volume/bioavailability (V/F) were 5.11 L/h and 41.6 L, respectively. Covariate analysis revealed that CL/F was significantly related to dosage, IMV use, and BSA. A simulation study showed that the 1600 mg/600 mg b.i.d. regimen was insufficient for the treatment of COVID-19 targeting the 50% effective concentration (9.7 microg/mL), especially in patients with larger BSA and/or IMV. A higher FPV dosage is required for COVID-19, but dose-dependent nonlinear pharmacokinetics may cause an unexpected significant pharmacokinetic change and drug toxicity. Further studies are warranted to explore the optimal FPV regimen.
  • |*COVID-19 Drug Treatment[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Amides/*administration & dosage/pharmacokinetics[MESH]
  • |Antiviral Agents/*administration & dosage/pharmacokinetics[MESH]
  • |COVID-19/blood[MESH]
  • |Chromatography, Liquid[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |Drug Administration Schedule[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Models, Theoretical[MESH]
  • |Pyrazines/*administration & dosage/pharmacokinetics[MESH]
  • |Retrospective Studies[MESH]
  • |Tandem Mass Spectrometry[MESH]


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