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

Tsai, Danny, Stewart, Penelope, Goud, Rajendra, Gourley, Stephen, Hewagama, Saliya, Krishnaswamy, Sushena, Wallis, Steven C., Lipman, Jeffrey and Roberts, Jason A. (2016) Total and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis. International Journal of Antimicrobial Agents, 48 6: 748-752. doi:10.1016/j.ijantimicag.2016.09.021


Author Tsai, Danny
Stewart, Penelope
Goud, Rajendra
Gourley, Stephen
Hewagama, Saliya
Krishnaswamy, Sushena
Wallis, Steven C.
Lipman, Jeffrey
Roberts, Jason A.
Title Total and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 1872-7913
0924-8579
Publication date 2016-12-01
Year available 2016
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1016/j.ijantimicag.2016.09.021
Open Access Status Not yet assessed
Volume 48
Issue 6
Start page 748
End page 752
Total pages 5
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Subject 2726 Microbiology (medical)
2736 Pharmacology (medical)
2725 Infectious Diseases
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. Crown Copyright (C) 2016 Published by Elsevier B.V. All rights reserved.
Formatted 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.
Keyword Critically ill
Indigenous
Pharmacokinetics
Severe sepsis
β-Lactam
Q-Index Code CX
Q-Index Status Provisional Code
Grant ID APP1074523
APP1048652
APP1099452
Institutional Status UQ

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
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