Pharmacokinetics of fluconazole in patients undergoing continuous ambulatory peritoneal dialysis

The pharmacokinetics of fluconazole given orally (100 mg) or intraperitoneally (50 and 150 mg) were determined in 15 patients with chronic renal failure who were undergoing continuous ambulatory peritoneal dialysis. The half-life (72 to 85 hours) was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied during an interhaemodialysis period. The peritoneal clearance, 0.26 to 0.33 L/h, led to an 18% recovery of administered drug in the dialysates after 48 hours. The peritoneal absorption was slow (time to peak plasma concentration 7 hours) but the peritoneal bioavailability was excellent at 87 +/- 5%. The mean concentrations of fluconazole up to 24 hours were 770 and 1900 micrograms/L after single intraperitoneal doses of 50 and 150 mg, respectively. The volume of distribution (40 to 60 L) did not differ from that determined in patients with normal renal function. In the case of fungal peritonitis essentially attributed to Candida spp., a 6-hour intraperitoneal infusion of fluconazole 150 mg every 2 days appears to be a good regimen to rapidly exceed minimum inhibitory concentrations and treat infection without risk of systemic dissemination of fungi or toxicity.