Furosemide binding to human albumin and plasma of nephrotic children.
The extent and nature of furosemide (F) binding to human albumin (HA) and to the plasma of 6 children with nephrotic syndrome were studied by equilibrium dialysis at 37 degrees C and pH 7.4 with 14C-F. At a total concentration of 3.4 mug/ml (therapeutic range), the unbound fraction of F to 4 gm per 100 ml HA was 2.79 plus or minus 0.35. The degree of binding was relatively constant from 1.8 to 36 mug/ml of F concentration. The percentage of unbound F doubled when total concentration of the drug was increased more than 130 times (1.8 to 245 mug/ml). F has two classes of binding sites (n1 = 1.42, k1 = 5.07 times 10-4 M-minus 1; n2 = 3.4, k2 = 1.58 times 10-4 M-minus 1); interaction with HA involves hydrophobic, ionic, and hydrogen forces. Acetylsalicylic acid (ASA), acetazolamide, diazoxide, phenylbutazone, sulfisoxazole (S), and tolbutamide (T) decreased F binding. Combinations of ASA, S, and T exerted a strong additive displacing effect. The binding of the F metabolite (4-chloro-5-sulfamoylanthranilic acid, CSA) was studied at 1.3 and 2.6 mug/ml. The unbound fraction was 5 times that of F. CSA did not influence F binding. Studies with plasma of 7 healthy adults showed that albumin is the only plasma protein responsible for F binding. The plasma albumin concentration range of the children with nephrotic syndrome was 0.6 to 2.1 gm per 100 ml. There was some correlation between albumin concentration and binding of F (2.8 to 9.6% unbound); this corresponded with findings with HA. Albumin concentrations lower than 2 gm per 100 ml seemed to influence the extent of the unbound fraction of F considerably.
D000086:Acetazolamide / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002648:Child; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood* / Q000188:drug therapy; D010653:Phenylbutazone / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism*; D013444:Sulfisoxazole / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
D010710:Phosphates; D012709:Serum Albumin; D013444:Sulfisoxazole; D005665:Furosemide; D014044:Tolbutamide; D010653:Phenylbutazone; D000086:Acetazolamide; D003981:Diazoxide; D001241:Aspirin