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Role of alpha‐1 acid glycoprotein, albumin, and nonesterified fatty acids in serum binding of apazone and warfarin
Author(s) -
Urien Saïk,
Albengres Edith,
Pinquier JeanLouis,
Tillement JeanPaul
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.119
Subject(s) - nefa , albumin , hypoalbuminemia , chemistry , warfarin , orosomucoid , serum albumin , medicine , fatty acid , endocrinology , pharmacology , drug , biochemistry , glycoprotein , atrial fibrillation
Altered concentrations of serum proteins and nonesterified fatty acids (NEFAs) often accompany malignant diseases. Free fractions (f u ) of apazone and warfarin were measured by equilibrium dialysis in serum samples obtained from 31 patients with cancer and 18 control subjects. Mean f u values of both drugs were significantly higher in the patient group. Multivariate analysis showed albumin, NEFA, and AAG for apazone and albumin, NEFA, and age for warfarin accounted for 60% and 63%, respectively, of interpatient variation in bound/free drug concentration ratios in the group of patients with cancer. The interactions of apazone and warfarin with AAG were further characterized; the more avid site had association constants of 4.5 × 10 5 and 2.3 × 10 5 L/mol, respectively. Finally, it is strongly suggested that when hypoalbuminemia is present and a drug binds to AAG with an affinity constant comparable to or higher than that to albumin, then f u will become dependent on the concentration of AAG. Clinical Pharmacology and Therapeutics (1986) 39, 683–689; doi: 10.1038/clpt.1986.119