G. Arredondo et al., PROTEIN-BINDING OF ITRACONAZOLE AND FLUCONAZOLE IN PATIENTS WITH CHRONIC-RENAL-FAILURE, International journal of clinical pharmacology and therapeutics, 32(7), 1994, pp. 361-364
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.