Stability and Compatibility of Levofloxacin, Clindamycin Phosphate, and Fluconazole in Various Peritoneal Solutions

Intraperitoneal administration of antibiotics is recommended for the treatment of peritoneal dialysis (PD)-related peritonitis. Antibiotics pre-added PD solution is commonly used for home-based treatment. Some antibiotics are recommended by ISPD for peritonitis treatment but does not have stability and compatibility data in different conditions yet. The current study was to investigate the stability and compatibility of such drugs.

Levofloxacin, clindamycin phosphate, and fluconazole were tested in the study. Three different commercially available PD solutions were selected. Two were glucose-based (2.5%, Ca 1.25 mmol/L, lactate buffered) solutions, one with PVC package and the other with non-PVC package. The third solution was icodextrin (non-PVC package). The stability of the three antibiotics was tested in the three different dialysates at different temperatures (4°C and 25°C) for 6 h, 1 day, 2 days, and 7 days. At 37°C, the storage stability was tested only for 6 h. The test antibiotics concentrations were selected as ISPD recommended or based on published data. All conditions were repeated separately in three bags. The antibiotics concentrations were measured by liquid chromatography-tandem mass spectrometry.

For clindamycin phosphate and fluconazole, there was no significant change in final concentration over the 7 days study period at both 4°C and 25°C. At 37°C, there was also no difference in concentration for clindamycin phosphate and fluconazole. For levofloxacin, there was no significant change in concentration over 7 days at 4°C. The concentration of levofloxacin was slightly higher after storage at 25°C and 37°C, while the exact differences were less than 3%. We noticed small but significant difference in drug concentrations for different solutions. It was generally lower in icodextrin than in glucose-based solutions. The exact differences were less than 10%. The difference between icodextrin and glucose-based solutions was higher than the two glucose-based solutions with different container material (PVC vs. non-PVC).

Levofloxacin, clindamycin phosphate, and fluconazole were stable and compatible with both glucose-based and icodextrin solutions. They might be stored for up to 7 days at room temperature (25°C). It is not suggested to store the dialysate for long time once warmed up to body temperature.