Pharmacokinetics of ciprofloxacin after intraperitoneal administration in uninfected patients undergoing CCPD

Abstract

Ciprofloxacin is increasingly used to treat peritoneal dialysis related peritonitis. We studied the pharmacokinetics of intraperitoneally administered ciprofloxacin in six uninfected CCPD patients. In a randomized cross-over setting ciprofloxacin was added either to a long dwell exchange (lastbag) or to four short dwell exchanges (dwell time 1.5 h). Addition of ciprofloxacin (25 mg/l) during the four short dwell exchanges resulted in dialysate levels of 21.1-13.3 mg/l during these exchanges. In the subsequent last bag devoid of ciprofloxacin a dialysate Cmax,D of 1.38 mg/l was observed at 30 min. Mean +/- SD serum Cmax,S was 0.59 +/- 0.29 mg/l after 5.4 h. Instillation of 100 mg/l ciprofloxacin in the last-bag yielded Cmax,D of 99.1 mg/l, falling with a t1/2 of 3.3 h towards levels < 2 mg/l at 19.8 h. A mean +/- SD serum Cmax,S of 0.69 +/- 0.19 was reached after 4 h. During four subsequent 1.5h exchanges without ciprofloxacin dialysate levels were < 0.1 mg/l. Instillation of 25 mg/l ciprofloxacin in the last-bag yielded a Cmax,D of 21.7 mg/l, falling towards levels < 2 mg/l at 15 h with a t1/2 of 3.85 h. A mean +/- SD serum Cmax,S of 0.26 +/- 0.03 was reached after 8 h. We conclude that the rapid absorption of ciprofloxacin from the dialysate into the tissues requires ciprofloxacin to be administered to all CCPD bags to ensure bactericidal dialysate levels. When therapeutic serum levels are required higher intraperitoneal doses or an oral or i.v. loading dose is warranted.