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The effect of disease, drugs, and dilution on the binding of sulfonamides in human plasma
Author(s) -
Anton Aaron H.
Publication year - 1968
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 - 10.1002/cpt196895561
Subject(s) - sulfonamide , chemistry , drug , plasma protein binding , dilution , sulfanilamide , human plasma , blood proteins , binding site , plasma concentration , pharmacology , chromatography , biochemistry , medicine , stereochemistry , physics , thermodynamics
The plasma protein‐binding capacity for sulfonamides (and presumably other drugs and endogenous substances) was found to be decreased more than 10 per cent in 4 of 16 hospitalized patients. 1n other experiments it was found that a combination of drugs significantly interfered with the protein binding of sulfonamides under conditions in which each drug by itself had only slight displacing activity. The drugs decreased the binding of the sulfonamides more when diluted plasma was used, and the interference was more marked when the drugs were tested against a less highly bound sulfonamide. It is suggested that a binding defect may contribute to the incidence of adverse reactions to drugs by making available unanticipated amounts of drug. In another series of experiments the binding of sulfonamides in human plasma was determined under the following conditions: (1) dilution of plasma protein while keeping sulfonamide concentration constant, and (2) dilution of a sulfonamide‐containing solution of plasma so as to maintain a constant ratio between protein and sulfonamide. As predicted by the law of mass action, the fraction of bound sulfonamide decreased in both situations as the protein was diluted. These results may explain the erroneous conclusion of several investigators who reported that the binding of sulfonamides in human serum did not interfere with antibacterial activity.