title: Protein binding of itraconazole and fluconazole in patients with cancer.
abstract: The serum protein binding of itraconazole and fluconazole, new azole antifungal agents, has been investigated in vitro, in serum from healthy volunteers and from patients with cancer. Protein binding was determined by ultrafiltration. Concentrations of both alpha 1-acid glycoprotein (AAG) and albumin (HSA) were measured in all serum samples. The serum protein 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 levels in cancer patients were significantly decreased (p < 0.01) and AAG levels were found to be significantly elevated in patients with respect to control subjects (p < 0.05). A significant linear relationship between the bound/unbound concentration ratio of itraconazole and HSA (r2 = 0.3340; p < 0.01) was found. Similarly, a significant relation was established between the bound/unbound concentration ratio of fluconazole and AAG levels (r2 = 0.2235; p < 0.05). Thus, a weak association between the binding of these drugs and serum protein levels has been observed. It is concluded that both antifungal drugs show different protein binding behaviour in cancer patients.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Basque Country, Leioa, Vizcaya, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Arredondo
authors.forename: R
authors.initials: R
authors.lastname: Calvo
authors.forename: F
authors.initials: F
authors.lastname: Marcos
authors.forename: R
authors.initials: R
authors.lastname: Martínez-Jordá
authors.forename: E
authors.initials: E
authors.lastname: Suarez
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000097:blood* / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood; D003110:Colonic Neoplasms / Q000097:blood; D004938:Esophageal Neoplasms / Q000097:blood; D005260:Female; D015725:Fluconazole / Q000097:blood*; D006801:Humans; D017964:Itraconazole / Q000097:blood*; D016014:Linear Models; D008175:Lung Neoplasms / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001798:Blood Proteins; D012709:Serum Albumin; D017964:Itraconazole; D015725:Fluconazole