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 iv dose 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] μg h/ml; AUMC((0-last)), 177.91 [11.1] and 91.9 [66.5] μg h(2)/ml; t(1/2β), 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.


CONCLUSIONS
In our patients we observed significant differences in some pharmacokinetic parameters of ciprofloxacin after two types of nephrectomy.
Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Sw. Marii Magdaleny 14, PL 61-861 Poznań, Poland. szalekedyta@wp.pl
Edyta
E
Szałek
Wojciech
W
Połom
Agnieszka
A
Karbownik
Tomasz
T
Grabowski
Agnieszka
A
Konkołowicz
Anna
A
Wolc
Marcin
M
Matuszewski
Kazimierz
K
Krajka
Edmund
E
Grześkowiak
D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000473:pathology / Q000601:surgery; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods*
D000890:Anti-Infective Agents; D002939:Ciprofloxacin