BACKGROUND: Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. OBJECTIVE: This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. DESIGN: The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. SETTING: The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. PATIENTS: Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). RESULTS: Peak plasma concentrations occurred at 2-3 hours with 0.35-1.35 microg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 microg/mL; PD clearance was 0.06 L/hr. CONCLUSION: Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.