Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Antimicrob Chemother. 2006 Aug;58(2):380-6. Epub 2006 May 30.

Which reliable pharmacodynamic breakpoint should be advised for ciprofloxacin monotherapy in the hospital setting? A TDM-based retrospective perspective.

Author information

  • 1Institute of Clinical Pharmacology & Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine 33100 Udine, Italy. federico.pea@med.uniud.it

Abstract

OBJECTIVES:

To define in critically ill patients receiving intravenous (iv) ciprofloxacin (200 mg or 400 mg twice daily) and undergoing routine therapeutic drug monitoring (TDM) the interindividual pharmacokinetic variability and the reliable pharmacodynamic breakpoint enabled by these fixed dosing regimens according to the PK/PD principles and to the pattern of susceptibility to this antibiotic.

METHODS:

Ciprofloxacin plasma concentrations [trough (Cmin) and 30 min post-dose peak (Cmax) levels] were analysed by means of an HPLC method. Optimal pharmacodynamic exposure was assessed by estimating the theoretical pharmacodynamic breakpoints (PD BP) for either Cmax or AUC.

RESULTS:

The final database included 177 sets of Cmin and Cmax performed in 89 patients (200 mg twice daily group, n=68; 400 mg twice daily group, n=21). A very wide interindividual scatter of results was observed for both the 200 mg group and the 400 mg group. Interestingly, for both groups only moderate log-linear relationships between estimated renal function (CLCR) on one hand and either Cmin (r2=0.08, 0.28) or estimated AUC24 (r2=0.10, 0.34) on the other hand were found. Median PD BP, respectively, in the 200 mg twice daily group and the 400 mg twice daily group, were 0.16 and 0.28 mg/L for Cmax, and 0.19 and 0.29 mg/L for AUC24.

CONCLUSIONS:

Lowering ciprofloxacin dosage in the presence of renal failure seems in most cases unnecessary, since drug accumulation occurred only in a few cases. Optimal pharmacodynamic exposure with fixed 200 or 400 mg twice daily regimens of ciprofloxacin may be ensured only against fully susceptible microorganisms with an MIC<0.3 mg/L. This supports the use of higher dosages in critically ill hospitalized patients, whereas the wide unpredictable interindividual pharmacokinetic variability suggests the usefulness of TDM with the intent of optimizing efficacy with ciprofloxacin therapy.

PMID:
16735422
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk