title: Ciprofloxacin pharmacokinetic profiles in paediatric sepsis: how much ciprofloxacin is enough?
abstract: OBJECTIVE
  To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with severe sepsis.
  
  
  METHODS
  Open and prospective.
  
  
  METHODS
  Tertiary referral multi-disciplinary ICU.
  
  
  METHODS
  Twenty patients (two groups - group A: 3 months-1 year; group B 1-5 years).
  
  
  METHODS
  Timed blood samples were taken for pharmacokinetics after the first dose (D(0)), as well as day 2 (D(2)) and then between days 6-8.
  
  
  RESULTS
  Ciprofloxacin serum levels were measured by high performance liquid chromatography. Demographic and clinical data and all adverse events were noted. Standard pharmacokinetic variables were calculated by non-compartmental methods. Peak concentrations (C(max)) for group A were D(0) 6.1+/-1.2 mg/l, D(2) 9.0+/-1.8 mg/l and D(7) 5.8+/-1.3 mg/l and, for group B, 7.4+/-1.3 mg/l, 7.8+/-1.6 mg/l and 6.4+/-1.3 mg/l, respectively, for the study periods. Concentration 12 h after the start of infusion (C(min)) for all periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A: 15.6+/-1.3, 19.2+/-1.63 and 14.1+/-1.4 mg/h per l, and group B: 15.9+/-1.3, 18.0+/-1.7 and 13.2+/-1.26 mg/h per l. One patient presenting with seizures, initially controlled, had another convulsion and a further patient developed seizures whilst on ciprofloxacin. C(max) in these patients were higher than the average C(max). The convulsions of both patients were easily controlled. No other drug-related serious adverse events occurred. No arthropathy was noted. Three patients died of their underlying disease.
  
  
  CONCLUSIONS
  There was no accumulation of drug even after 7 days of administration. Our C(max) and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms.
authors.affiliation: Intensive Care Facility, Royal Brisbane Hospital, Anaesthesiology and Critical Care, University of Queensland, Herston Road, Herston 4029, Brisbane, Queensland, Australia. j.lipman@mailbox.uq.edu.au
authors.forename: J
authors.initials: J
authors.lastname: Lipman
authors.forename: A G S
authors.initials: AG
authors.lastname: Gous
authors.forename: L R
authors.initials: LR
authors.lastname: Mathivha
authors.forename: S
authors.initials: S
authors.lastname: Tshukutsoane
authors.forename: J
authors.initials: J
authors.lastname: Scribante
authors.forename: H
authors.initials: H
authors.lastname: Hon
authors.forename: M
authors.initials: M
authors.lastname: Pinder
authors.forename: J F
authors.initials: JF
authors.lastname: Riera-Fanego
authors.forename: L
authors.initials: L
authors.lastname: Verhoef
authors.forename: H
authors.initials: H
authors.lastname: Stass
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D011446:Prospective Studies; D012640:Seizures / Q000139:chemically induced; D018805:Sepsis / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin