The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens

Br J Clin Pharmacol. 2013 Jan;75(1):180-5. doi: 10.1111/j.1365-2125.2012.04337.x.

Abstract

Aim: The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated.

Methods: In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\PHARM 3.60). A two compartment open model was used.

Results: Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively.

Conclusion: A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Infective Agents / pharmacokinetics*
  • Area Under Curve
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / adverse effects
  • Ciprofloxacin / pharmacokinetics*
  • Ciprofloxacin / pharmacology
  • Female
  • Hospitalization
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged

Substances

  • Anti-Infective Agents
  • Ciprofloxacin