Effect of total and partial nephrectomy on the elimination of ciprofloxacin in humans

Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer. Surgery is a standard procedure to resect the tumor during total (TN) or partial (nephron-sparing) nephrectomy (PN). Ciprofloxacin is most often administered at the usual intravenous dose of 100–400 mg/12 h. The application of such low doses of ciprofloxacin as 200 mg/24 h carries the risk of achieving subtherapeutic concentrations even in patients with limited renal function. The aim of the study was a comparison of concentrations and pharmacokinetics for ciprofloxacin at steady-state in patients after total and partial nephrectomy and evaluation of the effectiveness of the ivdose 200 mg/24 h against the theoretical value of MIC, 0.5 µg/ml. Methods: The research was carried out on two groups of patients after nephrectomy: total (group 1, n = 21; mean [SD], age, 62.9 [14.4] years; weight, 76.0 [14.6] kg; creatinine clearance, CL_CR, 90.7 [22.2] ml/min) and partial (group 2, n= 15; 61.7 [9.3] years; 87.8 [16.4] kg; CL_CR, 107.8 [36.4] ml/min). The patients were treated with ciprofloxacin in the dose of 200 mg/24 h (iv).Plasma concentrations of ciprofloxacin at steady state were measured with validated HPLC method with UV detection. Results: The mean values of plasma concentrations of ciprofloxacin at steady state in group 1 and 2 were: C^ss_max, 2.012 and 1.345; C^ss_min, 0.437 and 0.244 µg/ml, respectively. The main pharmacokinetic parameters for ciprofloxacin in group 1 and 2 were as follows: AUC_(0-last), 30.9 [17.9] and 19.5 [8.7] µgh/ml; AUMC_(0-last), 177.91 [11.1] and 91.9 [66.5] µgh²/ml; t_1/2ß, 13.9 [7.7] and 9.8 [3.3] h; MRT, 16.5 [12.1] and 9.77 [5.4] h; V_d, 115.0 [67.2] and 142.2 [78.7] l; CL, 6.2 [3.3] and 10.8 [5.7] l/h, respectively. With the assumed MIC = 0.5 µg/ml, the values of C^ss_max/MIC < 10 and AUC/MIC < 125 were obtained in all the patients. Conclusion: In our patients we observed significant differences in some pharmacokinetic parameters of ciprofloxacin after two types of nephrectomy.