The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients
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 recommend...
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Published in | Journal of antimicrobial chemotherapy Vol. 47; no. 4; pp. 421 - 429 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.04.2001
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | 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 pre-determined 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. |
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Bibliography: | PII:1460-2091 local:0470421 ark:/67375/HXZ-XR6BK4QF-F istex:3AC9751B491425EB0E73C4A28EBC8040AF70324B ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0305-7453 1460-2091 1460-2091 |
DOI: | 10.1093/jac/47.4.421 |