Time courses of netilmicin pharmacokinetics in patients with unilateral nephrectomy

Background: After unilateral nephrectomy, one remained kidney adapts morphologically and functionally in order to compensate the loss of opposite kidney. In this study, pharmacokinetics of netilmicin were repeatedly estimated to evaluate the time course of the renal functional changes on drug excretion after unilateral nephrectomy. Methods: After single or multiple doses of netilmicin (2.5 ± 0.3 mg/kg), two blood samples were drawn at 1 day before, 1, 3, 7 days and 3 months after operation in 42 subjects (27 patients with unilateral nephrectomy and 15 control patients with general urological operations). Pharmacokinetic parameters were estimated from nonlinear fittings of plasma netilmicin concentrations to one compartment model with using PCNONLIN. Results: The serum creatinine and creatinine clearance were significantly changed compared to those values before operation and to those of control subjects. Without any significant changes of extrapolated peak netilmicin concentrations, trough concentrations increased up to 2.0 folds of baseline level (0.41 ± 0.11 mg/L) at 7 days after unilateral nephrectomy. Total netilmicin clearance was gradually decreased and the plasma half-life was prolonged, and the maximum changes of them were observed at 7 days after nephrectomy (27.4 ± 5.8% and 48.7 ± 9.5% of baseline values 90.1 ± 5.4 ml/kg/hr and 2.6 ± 0.2 hr, respectively). All these pharmacokinetic changes of netilmicin were recovered to the baseline value at 3 months. The percent changes of netilmicin clearance showed good correlation with the serum creatinine concentration (r=0.50, p<0.01) and creatinine clearance (r= 0.47, p< 0.01). Conclusions: These results suggest that the renal function on drug excretion seems to change till months later after unilateral nephrectomy of a functional kidney and the close monitoring of a drug and/or metabolite excreted largely by kidney should be considered in the subject with very recent unilateral nephrectomy.