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10.1002/cpt.2196

http://scihub22266oqcxt.onion/10.1002/cpt.2196
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33547636!8013748!33547636
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suck abstract from ncbi


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pmid33547636      Clin+Pharmacol+Ther 2021 ; 109 (4): 1030-1033
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  • Neglecting Plasma Protein Binding in COVID-19 Patients Leads to a Wrong Interpretation of Lopinavir Overexposure #MMPMID33547636
  • Stanke-Labesque F; Concordet D; Djerada Z; Bouchet S; Solas C; Meriglier E; Bonnet F; Mourvillier B; Ruiz S; Martin-Blondel G; Epaulard O; Schwebel C; Gautier-Veyret E; Gandia P
  • Clin Pharmacol Ther 2021[Apr]; 109 (4): 1030-1033 PMID33547636show ga
  • Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in coronavirus disease 2019 (COVID-19) are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in patients with severe COVID-19 than those reported in patients with HIV. These findings have led to a reduction of the dose of lopinavir in some patients, hypothesizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID-19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse University Hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin, and alpha-1-acid glycoprotein (AAG) levels were measured during routine care on the same samples. In patients with COVID-19, increased total lopinavir concentration is the result of an increased AAG-bound lopinavir concentration, whereas the unbound concentration remains constant, and insufficient to reduce the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID-19, the description of lopinavir pharmacokinetics changes in COVID-19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration.
  • |*COVID-19 Drug Treatment[MESH]
  • |Aged[MESH]
  • |Albumins/metabolism[MESH]
  • |Antiviral Agents/*pharmacokinetics/therapeutic use[MESH]
  • |C-Reactive Protein/metabolism[MESH]
  • |Female[MESH]
  • |Glycoproteins/metabolism[MESH]
  • |Humans[MESH]
  • |Lopinavir/*pharmacokinetics/therapeutic use[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Plasma/*physiology[MESH]
  • |Protein Binding/*physiology[MESH]
  • |Retrospective Studies[MESH]
  • |SARS-CoV-2[MESH]


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