Single- and multiple-dose kinetics of ofloxacin in patients on continuous ambulatory peritoneal dialysis (CAPD).

Abstract

To evaluate the pharmacokinetics of ofloxacin, a novel quinolone antibiotic, in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD), we investigated 6 patients in a single-dose study and 9 patients in a multiple-dose study, all without peritonitis. In the single-dose study, patients received 200 mg ofloxacin orally. Serum concentrations (Cmax) peaked at 3.1 +/- 0.3 mg/L (mean +/- SEM), 1.6 +/- 0.5 h after p.o. administration of the drug. Elimination half-life (t1/2) was 26.8 +/- 2.5 h. Peritoneal clearance accounted for 10% of the total body clearance. After 5-h dwell time, ofloxacin concentrations in the dialysate were 1.5 +/- 0.2 mg/L, which is above the MIC90 for most bacteria responsible for peritonitis in patients on CAPD. In the multiple dose study, 200 mg ofloxacin were administered twice, with a time interval of 12 h, followed by 200 mg for 9 days every morning. Mean trough serum levels were 2.6 +/- 1.0 mg/L, mean peak concentrations were 4.1 +/- 1.7 mg/L. Mean ofloxacin concentrations in the peritoneal effluent were 1.9 +/- 0.9 mg/L. It is concluded that an oral loading dose of 400 mg on the first day and a maintenance dose of 200 mg ofloxacin/day does not lead to significant accumulation, even though the elimination by the peritoneal route is only small. The proposed dosing regimen could be an adequate therapy of peritonitis and exit-site infections in patients on CAPD since levels reached in the dialysate effluent are bactericidal. The clinical usefulness in the treatment of peritonitis has to be proven in further studies.