Population pharmacokinetics of ceftriaxone administered as continuous or intermittent infusion in critically ill patients

被引:22
|
作者
Leegwater, E. [1 ,2 ]
Kraaijenbrink, B. V. C. [3 ]
Moes, D. J. A. R. [4 ]
Purmer, I. M. [5 ]
Wilms, E. B. [1 ,2 ]
机构
[1] Apotheek Haagse Ziekenhuizen, The Hague, Netherlands
[2] Haga Teaching Hosp, Dept Pharm, The Hague, Netherlands
[3] Amsterdam Univ Med Ctr, Locat VUmc, Amsterdam, Netherlands
[4] Leiden Univ, Dept Clin Pharm & Toxicol, Med Ctr, Leiden, Netherlands
[5] Haga Teaching Hosp, Dept Intens Care, The Hague, Netherlands
关键词
INTENSIVE-CARE; PROTEIN-BINDING;
D O I
10.1093/jac/dkaa067
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: To describe the population pharmacokinetics and protein-binding characteristics of unbound ceftriaxone administered as continuous or intermittent infusion. Additionally, to determine the optimal dosing regimen in critically ill patients. Methods: A pharmacokinetic study was performed in the ICU of a tertiary teaching hospital. Patients were treated with ceftriaxone as continuous or intermittent infusion. A population pharmacokinetic model was developed with non-linear mixed-effects analysis. Subsequently, the PTA of a 100% T-> MIC was assessed for influential patient characteristics using Monte Carlo simulation. Results: Fifty-five patients were included. The pharmacokinetics of ceftriaxone was best described by a one-compartment model with non-linear saturable protein binding including the following covariates: body weight, estimated CLCR, serum albumin concentration and mode of administration. For pathogens with an MIC of 1 mg/L, the simulation demonstrated that intermittent infusion of 2 g/24 h only resulted in a >= 90% PTA in patients with a reduced CLCR (0-60 mL/min). Intermittent infusion of 2 g/12 h led to sufficient exposure if CLCR was 0-90 mL/min and continuous infusion of 2 g/24 h led to a >= 90% PTA in all simulations (CLCR 0-180 mL/min). Conclusions: In the critically ill, the clearance of unbound ceftriaxone is closely related to CLCR. Furthermore, ceftriaxone protein binding is saturable, variable and dependent on serum albumin concentration. Intermittent dosing of 2 g/24 h ceftriaxone leads to subtherapeutic exposure in patients with a normal or increased CLCR. Treating these patients with continuous infusion of 2 g/24 h is more effective than an intermittent dosing regimen of 2 g/12 h.
引用
收藏
页码:1554 / 1558
页数:5
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