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

2016-12

Tsai, Danny

Stewart, Penny

Goud, Rajendra

Gourley, Stephen

Hewagama, Saliya

Krishnaswamy, Sushena

Wallis, Steven C

Lipman, Jeffrey

Roberts, Jason A

Burns, Trauma & Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; Pharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia. Electronic address: d.tsai@uq.edu.au..

Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia..

Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia..

Emergency Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia..

Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; Department of Infectious Diseases, The Northern Hospital, Epping, Melbourne, Victoria, Australia..

Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; Monash Infectious Diseases, Monash Health, Clayton, Melbourne, Victoria, Australia..

Burns, Trauma & Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia..

Burns, Trauma & Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia..

Burns, Trauma & Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia..

Critically ill

Indigenous

Pharmacokinetics

Severe sepsis

β-Lactam

Adult

Anti-Bacterial Agents

Australia

Ceftriaxone

Chromatography

Critical Illness

Half-Life

Humans

Intensive Care Units

Microbial Sensitivity Tests

Middle Aged

Plasma

Population Groups

Prospective Studies

Protein Binding

Time Factors

Urine

Sepsis

Journal Article

Publication

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.

link

International journal of antimicrobial agents 2016-12; 48(6): 748-752

https://pubmed.ncbi.nlm.nih.gov/27838278/?otool=iaurydwlib