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Antimicrobial Agents and Chemotherapy, May 1996, 1153-1156, Vol 40, No. 5
JC Garrelts, G Jost, SF Kowalsky, GJ Krol and JT Lettieri
Many drugs exhibit altered pharmacokinetic parameters in burn patients. We
prospectively evaluated the pharmacokinetics of ciprofloxacin in eight burn
patients with active infections. Each patient received a 400- mg dose of
ciprofloxacin intravenously (i.v.) every 8 h, with each dose infused over 1
h by using a rate control device. Blood samples for analysis of plasma
ciprofloxacin concentrations, determined by high- performance liquid
chromatography, were obtained immediately predose, at the end of the
infusion, and 1, 2, 3, 4, 5, 6, and 7 h after the end of the infusion.
Urine was collected from 0 to 2, 2 to 4, and 4 to 8 h following the same
dose, and an aliquot was saved for determination of the ciprofloxacin
concentration. Urine was also collected for 24 h prior to this dose for
measurement of creatinine clearance (CLCR). Pharmacokinetic parameters were
estimated by noncompartmental analysis. Mean maximum and minimum plasma
ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55
microgram/ml, respectively. Mean values for clearance (CL), renal clearance
(CLR), volume of distribution, terminal elimination rate constant,
half-life (t1/2), and area under the concentration-time curve (AUC) were
29.1 +/- 17.5 liters/h, 13.5 +/- 10.1 liters/h, 1.75 +/- 0.41 liters/kg,
0.222 +/- 0.098 h-1, 4.5 +/- 3.9 h, and 20.7 +/- 16.6 micrograms.h/ml,
respectively. CL was higher and t1/2 was shorter than noted in previous
studies of acutely ill, hospitalized patients. A good correlation was noted
between creatinine clearance CL(CR) and both total ciprofloxacin CL (r =
0.85) and CLR (r = 0.84). A moderate inverse correlation was noted between
percent body surface area burned and total ciprofloxacin CL (r = -0.55). An
AUC/MIC ratio above 125 SIT-1 (where SIT is serum inhibitory titer), which
has been strongly correlated with clinical response and time to bacterial
eradication, was achieved in five of eight patients (63%) with a MIC of
0.25 microgram/ml. At a ciprofloxacin dosage of 400 mg i.v. every 12 h, an
AUC/MIC ratio above 125 SIT-1 would have been achieved in only two of eight
patients (25%). We conclude that ciprofloxacin CL is highly variable, but
generally increased, in burn patients compared with that in acutely ill,
general medical and surgical patients. Because of an increase in CL, a
ciprofloxacin dosage of 400 mg i.v. every 8 h is more likely to produce the
desired response in burn patients than the same dose given every 12 h.
Copyright © 1996 by the American Society for Microbiology. All rights reserved.
Ciprofloxacin pharmacokinetics in burn patients
Via Christi Regional Medical Center, University of Kansas, School of Medicine-Wichita, USA.
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