Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Beermann, B. et al.

Binding-site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells.

When 14C-chlorthalidone was administered orally to 2 healthy volunteers, the total recovery of radioactivity in urine (about 75 percent) and feces was close to 100 percent. Most of the label recovered in the blood was bound to the blood cells. When the procedure was repeated while the 2 subjects were receiving acetazolamide, the excretion of labeled material in urine and feces was essentially unchanged, but the blood cells contained less and the plasma more of the blood radioactivity. The half-life of the radioactivity in plasma and blood cells had decreased by about 65 percent. Intravenous administration of acetazolamide (single dose) to 2 other subjects who had received 14C-chlorthalidone orally resulted in a marked drop in the blood cell radioactivity, whereas that in plasma increased. The affinity of chlorthalidone for red blood cells was further evidenced on incubation of 14C-chlorthalidone with human blood. Of the incubated radioactivity, 94 percent to 99 percent was recovered in the erythrocytes. Preincubation of the blood samples with acetazolamide prior to the addition of 14C-chlorthalidone, as well as incubation of acetozolamide in blood samples previously incubated with 14C-chlorthalidone, demonstrated that acetazolamide is able to inhibit and to displace chlorthalidone from blood cells. There are several lines of evidence indicating that chlorthalidone is transported attached to the erythrocyte carbonic anhydrase.[1]

References

Binding-site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells. Beermann, B., Hellström, K., Lindström, B., Rosén, A. Clin. Pharmacol. Ther. (1975) [Pubmed]

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