Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis

Abstract

Background In order to avoid aminoglycosides, the International Society for Peritoneal Dialysis recommends cefazolin and ceftazidime for empirical treatment of peritonitis. Ciprofloxacin covers relevant gram-negative pathogens without the resistance associated with ceftazidime. However, ciprofloxacin pharmacokinetic data in patients on continuous cycling peritoneal dialysis (CCPD) are lacking. Objectives ( 1 ) To determine the pharmacokinetics of oral ciprofloxacin in CCPD patients, ( 2 ) to compare serum and dialysate ciprofloxacin concentrations with minimum inhibitory concentrations (MIC) of the gram-negative bacteria associated with peritonitis, and ( 3 ) to establish oral ciprofloxacin dosing guidelines for the empirical treatment of peritonitis in patients receiving CCPD. Methods Eligible CCPD patients received 2 doses of ciprofloxacin: 750 mg orally every 12 hours. Serial blood and end-of-dwell dialysate samples were collected during the first 12-hour interval; an end-of-dwell dialysate sample from the overnight dwell and a final blood sample were collected at the end of the second 12-hour interval. Ciprofloxacin concentrations were determined using a liquid chromatographic (HPLC)-fluorescence method. Pharmacokinetic calculations were completed assuming a one-compartment model. Results Eight patients completed the study. The pharmacokinetic parameters determined for ciprofloxacin were (mean ± SEM) serum half-life 10.1 ± 1.2 hours, maximum serum concentration 2.7 ± 0.5 mg/L, time to maximum serum concentration 1.6 ± 0.1 hours after the first dose, and peritoneal clearance 1.2% ± 0.1% of the mean calculated total body clearance. While all patients achieved serum area under the concentration-time curve: MIC > 125 for Escherichia coli and Klebsiella species after the first dose, only 2 patients achieved this goal for Pseudomonas aeruginosa. End-of-dwell dialysate concentrations were above the MIC for E. coli, Klebsiella spp, and P. aeruginosa after the second dose. Conclusion Ciprofloxacin 750 mg orally every 12 hours in CCPD patients may be useful for empirical gram-negative coverage of CCPD peritonitis and for treatment of documented peritonitis caused by sensitive E. coli or Klebsiella species. While ceftazidime may be required for documented pseudomonal peritonitis, the oral ciprofloxacin regimen achieved adequate serum concentrations to treat systemic gram-negative infections caused by sensitive E. coli or Klebsiella species.

ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment

“…Oral administration of fluoroquinolones is commonly used alone or in combination with other antibiotics ( 237 ). Oral ciprofloxacin and moxifloxacin reach adequate levels within the peritoneum ( 293 , 323 ). However, adequate IP levels may require a day to be reached, and some oral phosphate binders can bind fluoroquinolones and reduce their bioavailability ( 324 , 325 ).…”

“…Vancomycin can probably be given intermittently for APD patients. Oral ciprofloxacin can also achieve adequate levels within the peritoneum in APD patients ( 323 ). In a retrospective, single-center observational cohort study of 508 episodes of PD-associated peritonitis in 208 patients, no differences in relapse rates, mortality, or the combined end-point of mortality and catheter removal were observed between APD and CAPD patients continuing their own PD modality during continuous IP antibiotic treatment in each PD exchange, although elevated dialysis effluent leukocyte counts and antibiotic treatment durations were longer in the former ( 90 ).…”

Peritoneal Dialysis-Related Infections Recommendations: 2010 Update

“…The Committee recommends center-specific selection of empiric therapy, dependent on the local history of sensitivities of organisms causing peritonitis ( Opinion ). Gram-positive organisms may be covered by vancomycin or a cephalosporin, and gram-negative organisms by a third-generation cephalosporin or aminoglycoside ( Evidence ) (Figure 1) (65-105).…”

Pharmacokinetics and Bioequivalence Study of Two Ciprofloxacin Hydrochloride Tablets in Chinese Healthy Volunteers Under Fasting and Fed Conditions: A Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period, Single-Dose Crossover Study.

“…There were plenty of pharmacokinetics studies about cipro oxacin after a single dose oral administration of a cipro oxacin tablet in adult patients or healthy subjects, but most of studies on the pharmacokinetics of cipro oxacin mainly focused on the dose of 500 mg, the studies about a single dose of 250 mg were rare among them [14,[24][25][26][27][28][29][30][31][32][33]. Several previous studies indicated that the 250-mg singledose of cipro oxacin was e cacious and safe in the therapy of uncomplicated gonorrhea,equally to the 500-mg dose of cipro oxacin [7,[34][35][36][37], so it's meaningful to investigate the pharmacokinetics of a single dose of cipro oxacin 250 mg.…”