G. Arredondo et al., PROTEIN-BINDING OF ITRACONAZOLE AND FLUCONAZOLE IN PATIENTS WITH CANCER, International journal of clinical pharmacology and therapeutics, 33(8), 1995, pp. 449-452
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.