| Popis: |
The binding of eleven benzodiazepine derivatives to bovine serum albumin was determined by means of Sephadex gel filtration. The albumin binding of the substances was characterized by the percentage of drug bound, the binding constants k + , K 1 , and m , the number of binding sites per albumin molecule, and the free binding energy. The binding of the benzodiazepines to bovine serum albumin (BSA) is discussed in respect to the binding of these drugs to human serum albumin (HSA). The following great differences in the binding behaviour of both albumins for the benzodiaze-pines have been found: (1) The affinities of the binding of most of the drugs to BSA are exceptionally smaller than those to HSA. (2) Two benzodiazepines, lorazepam and clonazepam, are bound to BSA in a higher extent than to HSA. (3) Most of the benzodiazepines have two or three binding sites on the BSA molecule, in contrast to the single binding site on the HSA molecule. The binding of the benzodiazepines to BSA is positively influenced by the pH-value of the solution in a similar way as found for HSA. The benzodiazepines are the first group of drugs known in which binding to both albumins differs so fundamentally. The reason for these large differences and their pharmacological significance are discussed. |
