Total and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis

Danny Tsai, Penelope Stewart, Rajendra Goud, Stephen Gourley, Saliya Hewagama, Sushena Krishnaswamy, Steven C. Wallis, Jeffrey Lipman, Jason A. Roberts

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

In the absence of specific data to guide optimal dosing, this study aimed to describe the pharmacokinetics of ceftriaxone in severely septic Australian Indigenous patients and to assess achievement of the pharmacodynamic target of the regimens prescribed. A pharmacokinetic study was conducted in a remote hospital intensive care unit in patients receiving ceftriaxone dosing of 1 g every 12 h (q12h). Serial blood and urine samples were collected over one dosing interval on two consecutive days. Samples were assayed using a validated chromatography method for total and unbound concentrations. Concentration–time data collected were analysed with a non-compartmental approach. A total of 100 plasma samples were collected from five subjects. Ceftriaxone clearance, volume of distribution at steady-state, elimination half-life and elimination rate constant estimates were 0.9 (0.6–1.5) L/h, 11.2 (7.6–13.4) L, 9.5 (3.2–10.2) h and 0.07 (0.07–0.21) h–1, respectively. The unbound fraction of ceftriaxone ranged between 14% and 43%, with a higher unbound fraction present at higher total concentrations. The unbound concentrations at 720 min from the initiation of infusion for the first and second dosing intervals were 7.2 (4.8–10.7) mg/L and 7.8 (4.7–12.1) mg/L respectively, which exceeds the minimum inhibitory concentration of all typical target pathogens. In conclusion, the regimen of ceftriaxone 1 g q12h is adequate for critically ill Australian Indigenous patients with severe sepsis caused by non-resistant pathogens.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume48
Issue number6
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

Keywords

  • Critically ill
  • Indigenous
  • Pharmacokinetics
  • Severe sepsis
  • β-Lactam

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