Single and Multiple-Dose Kinetics of Ofloxacin in Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)

Abstract

To evaluate the pharmacokinetics of ofloxacin, a novel quinolon antibiotic, in patients with end-stage renal disease (ESRO) on continuous ambulatory peritoneal dialysis (CAPO), 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 (x ± SEM), 1.6 ± 0.5 h after p. 0. administration of the drug. Elimination half-life ( t112) 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 CAPO. 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 CAPO since levels reached in the dialysate effluent are bactericidal. The clinical usefulness in the treatment of peritonitis has to be proven in further studies.

Risk Factors and Outcome of Contamination in Patients on Peritoneal Dialysis—A Single-Center Experience of 15 Years

“…Prior studies have described a vast diversity of microorganisms related to touch contamination in PD systems (4), and hence the antibiotics used for prophylaxis should cover both the gram-positive and the gram-negative spectrum. We chose levofloxacin as the prophylactic agent because it is easy to administer and provides good coverage for common gram-positive and -negative organisms, with good penetration into peritoneal fluid (5). Previous studies at our unit had verified that adequate levels for treating peritonitis could be achieved with oral ofloxacin in a 400 mg loading dose, followed by 300 mg daily (6,7).…”