Pharmacokinetics of fluoroquinolones in uncompensated cirrhosis: the significance of penetration in the ascitic fluid

In order to study the penetration of routinely used fluoroquinolones in the ascitic fluid of patients with uncompensated cirrhosis the following doses were given. Three patients received three consecutive iv doses of 200 mg of ciprofloxacin, six patients, three consecutive iv doses of 300 mg of ciprofloxacin, seven others, three consecutive iv doses of 400 mg of pefloxacin and six, three consecutive iv doses of 400 mg of ofloxacin. Drug levels in serum and the ascitic fluid were monitored at regular time intervals. Peak levels of the 200 mg dose of ciprofloxacin, of the 300 mg dose of ciprofloxacin, of pefloxacin and of ofloxacin in serum were 2.11, 2.45, 9.21 and 8.86 mug/ml, respectively and in the ascitic fluid 0.67, 0.45. 6.09 and 5.83 mug/ml, respectively T-1/2 was 3.19 +/- 0.73, 3.55 +/- 1.68, 15.60 +/- 12.40 and 9.45 +/- 3.14 h, respectively with AUC of 3.62 +/- 4.02, 7.39 +/- 4.70, 137.85 +/- 63.96 and 119.8 +/- 16.83 mg/l h. Urinary excretion of ciprofloxacin and of ofloxacin was similar to healthy individuals but pefloxacin showed a mean urinary excretion of 30.11%. It is concluded that pefloxacin and ofloxacin at the administered iv doses result in serum and ascitic fluid levels above the MICs of the common pathogens causing spontaneous bacterial peritonitis and that they should be administered to cirrhotic patients in dosing regimens similar to those in patients with normal hepatic function. The use of ciprofloxacin requires further studies to define the appropriate dose. (C) 2001 Published by Elsevier Science B.V. and International Society of Chemotherapy.