Ketoconazole Pharmacokinetics in Continuous Ambulatory Peritoneal Dialysis

Abstract

Ketoconazole, a new oral drug, has minimal toxicity and a broad spectrum of antifungal activity. To determine its usefulness in fungal peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD), we carried out nine pharmacokinetic studies in five patients on CAPD. Serum levels of ketoconazole in CAPD patients were lower than in normal controls, and some patients did not appear to absorb the drug. We did not detect ketoconazole in the peritoneal fluid of any patient, even in the presence of peritoneal inflammation. One should not use this agent in the treatment of fungal peritonitis at daily doses of 400 mg or less because such a dose achieves only poor peritoneal fluid concentrations. Continuous ambulatory peritoneal dialysis (CAPD) has become an attractive alternative to hemodialysis for many patients with chronic renal failure. However, a major drawback with this technique is peritonitis (1). Although most of these infections are due to staphylococci (I), fungal peritonitis appears to be increasing as experience with CAPD grows (2,3). The treatment of such peritonitis is hampered by the poor penetration of amphotericin B into the peritoneal fluid (2), chemical peritonitis when amphotericin B is instilled directly into the cavity (3), and the limited spectrum of activity of flucytosine -a drug which readily penetrates into the peritoneal fluid (4). Ketoconazole is less toxic than amphotericin B and easier to administer and it has a much broader antifungal spectrum than flucytosine. The value of ketoconazole in fungal peritonitis remains to be established, and we have only limited data concerning its penetration into the peritonal cavity (2, 5). In this study we assessed the serum and peritoneal-fluid levels of ketoconazole in patients on CAPD.