The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients

Joynt, G. M., Lipman, J., Gomersall, C. D., Young, R. J., Wong, E. L. Y. and Gin, T. (2001) The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients. Journal of Antimicrobial Chemotherapy, 47 4: 421-429. doi:10.1093/jac/47.4.421


Author Joynt, G. M.
Lipman, J.
Gomersall, C. D.
Young, R. J.
Wong, E. L. Y.
Gin, T.
Title The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2001-04
Sub-type Article (original research)
DOI 10.1093/jac/47.4.421
Volume 47
Issue 4
Start page 421
End page 429
Total pages 9
Editor M. J. Wood
Place of publication London
Publisher Oxford University Press
Collection year 2001
Language eng
Subject C1
320500 Pharmacology and Pharmaceutical Sciences
730100 Clinical (Organs, Diseases and Abnormal Conditions)
Abstract The aim of this study was to determine the pharmacokinetic profile of the normal recommended dose of ceftriaxone in critically ill patients and to establish whether the current daily dosing recommendation maintains plasma concentrations adequate for antibacterial efficacy. Ceftriaxone at a recommended dose of 2 g iv was administered od to 12 critically ill patients with severe sepsis and normal serum creatinine concentrations. Blood samples were taken at predetermined intervals over the first 24 h and on day 3 for measurement of ceftriaxone concentrations. There was wide variability in drug disposition, explained by the presence of variable renal function and identified by the measurement of creatinine clearance. In nine patients with normal renal function, there was a high level of creatinine clearance(mean +/- S.D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which resulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with normal subjects, ceftriaxone clearance was increased 100%, volume of distribution increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients correlates with renal clearance by glomerular filtration. The elimination half-life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal failure when compared with previously published data in non-critically ill patients with renal failure. We conclude that in critically ill patients with normal renal function, inadequate plasma concentrations may result following od bolus dosing of ceftriaxone. Drug accumulation may occur in critically ill patients with renal failure.
Keyword Infectious Diseases
Microbiology
Pharmacology & Pharmacy
Plasma-protein Binding
Intensive-care Unit
Pseudomonas-aeruginosa
Continuous-infusion
Antibacterial Activity
Hemorrhagic-shock
Therapeutic Use
Ceftazidime
Model
Parameters
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 14 Aug 2007, 15:58:18 EST