Binding of hydrochlorothiazide to erythrocytes

Journal of Pharmacobio-dynamics
M YamazakiY Orita


Hydrochlorothiazide (HCT) was administered orally to healthy volunteers and intravenously to rabbits. HCT concentrations in plasma (Cp) and erythrocytes (Ce) were determined by a high-performance liquid chromatographic method. Ce was about 9-fold that of Cp 24 h after the administration to volunteers, and 8-fold 6 h after the administration to rabbits. From the results of the in vitro binding study which was done with rabbit erythrocytes, at least the presence of three kinds of binding site for HCT was expected. The first binding site was characterized by extremely high affinity and very low capacity, and was unaffected by acetazolamide, known as a carbonic anhydrase inhibitor. The second one was characterized by medium affinity and medium capacity, and disappeared under the presence of acetazolamide and may be due to the carbonic anhydrase of erythrocytes. The third one was characterized by low affinity, but its binding capacity was extremely high and apparently unsaturable in the HCT concentration range studied (0.5-100 micrograms/ml = 1.68-336 microM). The binding of HCT to erythrocytes seems to be dominated by the second binding site in the therapeutic range (under 1 microgram/ml of plasma).

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