PROTEIN-BINDING OF ITRACONAZOLE AND FLUCONAZOLE IN PATIENTS WITH CHRONIC-RENAL-FAILURE

The serum protein binding of itraconazole and fluconazole, new triazol e antifungal agents, has been investigated in vitro in the serum of he althy volunteers and in patients with chronic renal failure (predialys is). Protein binding was determined by ultrafiltration. Concentrations of both alpha1-acid glycoprotein (AAG) and albumin were measured in a ll serum samples. The protein binding of itraconazole showed no signif icant changes in patients with chronic renal failure when compared to healthy volunteers (96.64 +/- 0.99% vs. 96.85 +/- 0.33%). In contrast, fluconazole protein binding was significantly increased in the same p atients (22.91 +/- 6.15% vs. 12.51 +/- 2.37%; p < 0.001). In addition, whereas albumin levels in the latter patients were significantly decr eased (p < 0.001), their AAG levels were found to be significantly ele vated with respect to control subjects (p < 0.001). While no correlati on was established between itraconazole protein binding and albumin or AAG concentrations, a significant correlation was found between fluco nazole protein binding and AAG levels (r = 0.72; p < 0.001). Fluconazo le protein binding was found to be independent of albumin concentratio ns. In vitro carbamylation of serum protein with potassium cyanate cau sed no changes in the protein binding of fluconazole or itraconazole. We conclude that the binding of itraconazole by serum proteins is not altered in diseases involving changes of AAG or albumin concentrations . However, fluconazole protein binding may be altered in disease state s associated with increased AAG concentrations.