INFLUENCE OF RENAL-FAILURE ON CIPROFLOXACIN PHARMACOKINETICS IN RATS

Ciprofloxacin pharmacokinetics have been shown to be modified in patie nts with renal failure (e.g., the intestinal secretion of ciprofloxaci n is increased). This study investigated the influence of renal failur e on the pharmacokinetics of ciprofloxacin following oral and parenter al administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CLR) was reduced in n ephrectomized rats (5.3 +/- 1.4 versus 17.8 +/- 4.7 ml/min/kg, P < 0.0 1, nephrectomized versus control rats), However, nonrenal clearance wa s increased in nephrectomized rats (32 +/-: 4 versus 15 +/- 5 ml/min/k g, P < 0.01, nephrectomized versus control rats), suggesting compensat ory mechanisms for reduced renal function. After oral administration, apparent total clearance and CLR were reduced (P < 0.01) in nephrectom ized rats (117 +/- 25 and 6.8 +/- 4.4 ml/min/kg, respectively) compare d with the values for control rats (185 +/- 9 and 22.6 +/- 5.3 ml/min/ kg, respectively) and the area under the concentration-time curve was higher (P < 0.01) for nephrectomized rats (436.3 +/- 90.5 mg min/liter ) than for control rats (271.3 +/- 14.3 mg.min/liter). Terminal elimin ation half lives in the two groups remained constant after oral and pa renteral administration/ These results suggest an increased bioavailab ility of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.