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Antimicrobial Agents and Chemotherapy, February 1998, p. 289-292, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

B. Nouaille-Degorce,1 C. Veau,1,2 S. Dautrey,1 M. Tod,3 D. Laouari,4 C. Carbon,5 and R. Farinotti1,2,*

Service de Pharmacie Clinique et des Biomatériaux,1 INSERM U426,4 and INSERM U13,5 G. H. Bichat-C. Bernard, 75018 Paris, and Laboratoire de Pharmacie Clinique, Faculté de Pharmacie de Paris XI, 92290 Chatenay Malabry,2 and Service de Pharmacologie et de Toxicologie, Hôpital d'Avicenne, 93 Bobiny,3 France

Received 28 March 1997/Returned for modification 19 September 1997/Accepted 15 November 1997

Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CLR) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg, P < 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg, P < 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CLR were reduced (P < 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared 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 elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.

* Corresponding author. Mailing address: Service de Pharmacie Clinique et des Biomatériaux, G. H. Bichat-C. Bernard, 46, rue Henri Huchard, 75018 Paris, France. Phone: 33-1-40-25-80-05. Fax: 33-1-42-63-58-25. E-mail: robert.farinotti{at}bch.ap_hop_paris.fr.

Antimicrobial Agents and Chemotherapy, February 1998, p. 289-292, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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