CIPROFLOXACIN PHARMACOKINETICS IN BURN PATIENTS

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 40 0-mg dose of ciprofloxacin intravenously (i.v.) every 8 h, with each d ose infused over 1 h by using a rate control device. Blood samples for analysis of plasma ciprofloxacin concentrations, determined by high-p erformance liquid chromatography, were obtained immediately predose, a t 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 (CL(CR)). P harmacokinetic parameters were estimated by noncompartmental analysis. Mean maximum and minimum plasma ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55 mu g/ml, respectively. Mean values for clea rance (CL), renal clearance (CL(R)), volume of distribution, terminal elimination rate constant, half-life (t(1/2)), and area under the conc entration-time curve (AUG) 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 mu g . h/ml, respectively. CL was higher and t(1/ 2) was shorter than noted in previous studies of acutely ill, hospital ized patients. A good correlation was noted between creatinine clearan ce (CL(CR)) and both total ciprofloxacin CL (r = 0.85) and CL(R) (r = 0.84). A moderate inverse correlation was noted between percent body s urface 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 mu g/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 v ariable, but generally increased, in burn patients compared with that in acutely ill, general medical and surgical patients. Because of an i ncrease 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.