Multiple-dose-kinetics of ofloxacin after intraperitoneal application in CAPD patients

Pharmacokinetics of ofloxacin in plasma and peritoneal fluid were studied in 11 patients on continuous ambulatory peritoneal dialysis (CAPD). Seven patients without peritonitis received 20 mg ofloxacin added to 2L dialysate i.p. every 6 h for one day only, while 4 patients with acute peritonitis were treated with this same dosage every 4 h for 3 days, then every 6 h for the next 7 days. Ofloxacin concentrations in plasma and dialysate were determined by HPLC. After i.p. drug application there was a rapid elimination of ofloxacin from dialysate, this being significantly faster in patients with peritonitis as compared to those without. Likewise, the total amount lost from the first bag after a 3 h dwell was higher in the peritonitis group (84.7 +/- 1.5%; mean +/- SEM) than in the non-peritonitis group (75.6 +/- 2.1%). Twenty-four h after start of ofloxacin treatment, the mean peritoneal fluid concentrations at the end of each exchange studied were all above 3 mg/L. In patients with peritonitis, plasma concentrations of ofloxacin rose to 0.94 +/- 0.05 mg/L after 24 h reaching a Cmax of 1.8 +/- 0.2 mg/L after a tmax of 84 +/- 23 h. Intraperitoneal administration of ofloxacin was well tolerated, and no local or systemic adverse events were observed. Peritonitis episodes that were caused by Staphylococcus epidermidis (3) and by E. coli (1) were cured in all patients.