Comparative polymyxin B pharmacokinetics in critically ill patients with renal insufficiency and in continuous veno-venous hemodialysis.

Purpose: The aim of this study was to assess polymyxin B pharmacokinetics (PK) in patients with varying degrees of renal dysfunction and in patients who require continuous veno-venous hemodialysis (CVVHD). Methods: The study enrolled 37 patients with sepsis, including 13 patients with glomerular fil...

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Publicado en:European Journal of Clinical Pharmacology Vol. 79; no. 1; pp. 79 - 88
Autores principales: Surovoy, Yury A., Burkin, Maksim A., Galvidis, Inna A., Sobolev, Mikhail A., Rende, Onur Can, Tsarenko, Sergei V.
Formato: equations & formulas research tables/charts Journal Article
Publicado: Springer Nature Jan2023
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jan2023
      vid: 79
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-022-03415-x
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        atl: Comparative polymyxin B pharmacokinetics in critically ill patients with renal insufficiency and in continuous veno-venous hemodialysis.
      aug:
        au:
          Surovoy, Yury A.
          Burkin, Maksim A.
          Galvidis, Inna A.
          Sobolev, Mikhail A.
          Rende, Onur Can
          Tsarenko, Sergei V.
        affil: I.I. Mechnikov Research Institute for Vaccines and Sera, 105064, Moscow, Russia
      sug:
        subj:
          Renal Insufficiency Drug Therapy
          Sepsis Drug Therapy
          Polymyxin B Pharmacokinetics
          Antibiotics Pharmacokinetics
          Continuous Venovenous Hemodialysis Methods
          Critically Ill Patients Psychosocial Factors
          Human
          Male
          Female
          Middle Age
          Aged
          Glomerular Filtration Rate
          Polymyxin B Blood
          Enzyme-Linked Immunosorbent Assay
          Descriptive Statistics
          Data Analysis Software
          T-Tests
          Mann-Whitney U Test
          Chi Square Test
          Middle Aged: 45-64 years
          Aged: 65+ years
          Male
          Female
      ab: Purpose: The aim of this study was to assess polymyxin B pharmacokinetics (PK) in patients with varying degrees of renal dysfunction and in patients who require continuous veno-venous hemodialysis (CVVHD). Methods: The study enrolled 37 patients with sepsis, including 13 patients with glomerular filtration rate (GFR) below 80 mL/min and 11 patients on CVVHD. Each patient received a loading dose of polymyxin B (200–300 mg) and at least 3 subsequent doses of 100–150 mg every 12 h. For every patient, 6–8 blood samples were collected between doses. Polymyxin B (PMB) serum concentration was determined using enzyme-linked immunosorbent assay. Results: In sepsis, patients with preserved renal function mean area under the curve over 24 h (AUC0–24 h) value reached 67.8 ± 9.8 mg*h/L, while in patients with GFR below 80 mL/min, mean AUC0–24 h was 87 ± 5.8 mg*h/L. PMB PK in patients with renal insufficiency was characterized by significantly lower clearance (CL) compared to the normal renal function group (2.1 ± 0.1 L/h vs 3.9 ± 0.4 L/h respectively). In patients on CVVHD, mean AUC0–24 h was 110.4 ± 10.3 mg*h/L, while CL reached 2 ± 0.23 L/h. The median recovery rate from dialysate constituted 22%. Simulation of different dosage regimens that indicate a fixed maintenance dose of 100 mg q12h with a loading dose of 200 mg is optimal for patients on CVVHD, and no dosage increase is required. Conclusion: This study demonstrates decreased clearance of PMB in patients with renal insufficiency, which puts them at risk of toxicity. Therefore, patients with extremes of renal function might benefit from therapeutic drug monitoring. For patients with anuria, who require CVVHD, we suggest a fixed dose of 100 mg q12h.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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