PMID: 2498861Mar 1, 1989Paper

Binding of sulfonamides to carbonic anhydrase: influence on distribution within blood and on pharmacokinetics

Pharmaceutical Research
A BoddyM Rowland

Abstract

Four new aromatic sulfonamides were synthesized and purified by standard techniques. Two were unsubstituted, primary sulfonamides and two possessed substituents on the sulfonamide nitrogen. The affinity of the inhibitors for the enzyme carbonic anhydrase was determined in terms of the inhibitory potency, which was found to be dependent on the presence of an unsubstituted sulfonamide group. Binding studies were performed in erythrocyte suspensions using a range of concentrations and the unbound, extracellular concentrations were determined by high-performance liquid chromatographic (HPLC) assay. The dissociation constant of binding and the total binding capacity of the erythrocytes were estimated by nonlinear regression using a two-site binding model. The affinity of the compounds for erythrocytes reflected their inhibitory potency against the enzyme. Binding to plasma proteins was more dependent on lipophilicity and pKa and was stronger for the substituted sulfonamides. Pharmacokinetic studies in rats showed that the unsubstituted sulfonamides with a high affinity for carbonic anhydrase in erythrocytes have longer half-lives and lower clearance values than the substituted sulfonamides which were more strongly bound to plasma pr...Continue Reading

Citations

Dec 1, 1996·The Journal of Pharmacy and Pharmacology·I IeiriS Higuchi
Nov 15, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Rhys M Jones, Anthony Harrison
May 23, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Philip GardinerKen Grime

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