Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing

Lipman, Jeffrey, Wallis, Steven C., Rickard, Claire M. and Fraenkel, David (2001) Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing. Intensive Care Medicine, 27 2: 363-370. doi:10.1007/s001340000741


Author Lipman, Jeffrey
Wallis, Steven C.
Rickard, Claire M.
Fraenkel, David
Title Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing
Journal name Intensive Care Medicine   Check publisher's open access policy
ISSN 0342-4642
1432-1238
Publication date 2001-02
Sub-type Article (original research)
DOI 10.1007/s001340000741
Volume 27
Issue 2
Start page 363
End page 370
Total pages 8
Editor K. J. Falke
Place of publication Berlin
Publisher Sringer-Verlag
Collection year 2001
Language eng
Subject C1
320500 Pharmacology and Pharmaceutical Sciences
730100 Clinical (Organs, Diseases and Abnormal Conditions)
111502 Clinical Pharmacology and Therapeutics
110310 Intensive Care
Formatted abstract
Objectives: To measure plasma levels and pharmacokinetics of cefpirome in critically ill septic patients with normal renal function. To use the pharmacokinetic model to simulate alternate dosing regimens and identify those that predict sustained levels. Design and setting: A prospective, open-label, descriptive study in a 22-bed, multidisciplinary, adult ICU in a university-affiliated, tertiary referral hospital. Patients: Twelve adults with normal renal function on enrolment and with suspected or documented sepsis in whom cefpirome was judged to be the appropriate therapy by the managing clinician. Interventions: Cefpirome 2 g was infused intravenously over 3 min every 12 h. Timed blood samples were taken prior to and during two dosing intervals. Urine was collected for creatinine clearance determination. Measurements and results: Two patients were non-evaluable due to renal dysfunction post-enrolment. The median cefpirome trough level was 1.1 mg/l (range 0.5-8.1 mg/l) after the initial dose and 1.4 mg/l (range <0.5-15.9 mg/l) at 'steady state'. The volumes of distribution and elimination half-lives were greater and more variable than in healthy volunteers. Pharmacokinetic simulation predicted that more frequent bolus dosing, increased doses and continuous infusions would result in concentrations greater than 4 mg/l for over 60% of the dosing interval for all patients. Conclusions: Cefpirome 2 g twice daily produced low plasma troughs in a number of patients. Our data suggest that this drug regimen may be inadequate for successful treatment of difficult-to-treat infections in critically ill patients with normal renal function.
Keyword Critical Care Medicine
Antibiotics
Pseudomonas Infections
Pharmacokinetics
Cefpirome
Critically Ill
Beta-lactam Infusions
Intensive-care Patients
Organ Failure
Pseudomonas-aeruginosa
Intermittent Infusion
Protein-binding
Ceftazidime
Amikacin
Pharmacodynamics
Ciprofloxacin
Infections
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, 15:58:10 EST