The effect of direct hemoperfusion with polymyxin B immobilized cartridge on meropenem in critically ill patients requiring renal support

J Crit Care. 2019 Jun;51:71-76. doi: 10.1016/j.jcrc.2019.02.007. Epub 2019 Feb 5.

Abstract

Purpose: To evaluate the effect of direct hemoperfusion with polymyxin B immobilized cartridge (DHP-PMX) on meropenem pharmacokinetics in critically ill patients with sepsis requiring continuous venovenous hemofiltration (CVVH).

Material and methods: After intravenous infusion of 1 g meropenem over 3 h repeated every 8 h for at least 3 doses, 2 serial blood and ultrafiltration fluid samples were collected: one over a dose interval of meropenem with DHP-PMX therapy; and the other on the following day over a dose interval of meropenem with no DHP-PMX therapy. Meropenem concentrations were measured by high performance liquid chromatography. Pharmacokinetic parameters of meropenem and extraction ratio of DHP-PMX were calculated.

Results: Mean AUC0-8 of meropenem on DHP-PMX day was comparable to that of the DHP-PMX free day (285.2 ± 138.2 vs 297.8 ± 130.2 mg ∗ h/L; paired t-test, p = .618). No statistical significance of peak and trough concentrations, volume of distribution, sieving coefficient, or half-life were found. Extraction ratio of DHP-PMX on meropenem was 0 [0-0.03] and clearance by DHP-PMX was 0.04 [0-0.2] L/h which was not considered clinically significant.

Conclusions: No significant effect of DHP-PMX on meropenem pharmacokinetics was observed among severe sepsis/septic shock patients during CVVH treatment.

Trial registration: Clinical Trial Registry detail: NCT registry: 02413541 (First registered March 3, 2015, last update October 16, 2017).

Trial registration: ClinicalTrials.gov NCT02413541.

Keywords: Continuous venovenous hemofiltration; Hemoperfusion; Meropenem; Polymyxin B immobilized cartridge.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Critical Illness
  • Female
  • Hemoperfusion / methods
  • Humans
  • Infusions, Intravenous
  • Kidney Failure, Chronic*
  • Male
  • Meropenem / metabolism*
  • Middle Aged
  • Polymyxin B / administration & dosage
  • Polymyxin B / pharmacology*
  • Prospective Studies
  • Shock, Septic*
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Meropenem
  • Polymyxin B

Associated data

  • ClinicalTrials.gov/NCT02413541