Ketoconazole kinetics in chronic peritoneal dialysis

The kinetics of oral ketoconazole in serum and peritoneal fluid were studied in six patients with renal failure receiving peritoneal dialysis. A dose of 400 mg ketoconazole resulted in a maximum blood concentration of 2.3 +/- 1.7 microgram/ml (mean +/- SD), which occurred 3.3 +/- 1.6 hours after dosing. The serum t1/2 was 2.4 +/- 0.8 hours. Peritoneal clearance values were less than 1 ml/min, and peritoneal penetration reached 3.4% of the serum concentration by 5 hours. Protein binding studies were also performed. Compared with healthy controls, patients receiving peritoneal dialysis have significantly less ketoconazole serum protein binding. Fifty to eighty percent of the drug is protein bound in the peritoneal fluid, and the unbound concentration is in the same range as that in the serum of healthy individuals with "therapeutic" total ketoconazole levels of 1 to 2 micrograms/ml.