PROTEIN-BINDING OF ITRACONAZOLE AND FLUCONAZOLE IN PATIENTS WITH CANCER

The serum protein binding of itraconazole and fluconazole, new azole a ntifungal agents, has been investigated in vitro, in serum from health y volunteers and from patients with cancer. Protein binding was determ ined by ultrafiltration. Concentrations of both al-acid glycoprotein ( AAG) and albumin (HSA) were measured in all serum samples. The serum p rotein binding of itraconazole was reduced in patients (96.02 +/- 1.41 % vs 97.25 +/- 0.54%; p < 0.01) with respect to healthy volunteers. In contrast, fluconazole protein binding was increased in the same group of patients (22.96 +/- 3.60% vs 13.30 +/- 2.58%; p < 0.01). HSA level s in cancer patients were significantly decreased (p < 0.01) and AAG l evels were found to be significantly elevated in patients with respect to control subjects (p < 0.05). A significant linear relationship bet ween the bound/unbound concentration ratio of itraconazole and HSA (r( 2) = 0.3340; p < 0.01) was found. Similarly, a significant relation wa s established between the bound/unbound concentration ratio of flucona zole and AAG levels (r(2) = 0.2235; p < 0.05). Thus, a weak associatio n between the binding of these drugs and serum protein levels has been observed. It is concluded that both antifungal drugs show different p rotein binding behaviour in cancer patients.