Diminishing Effect of Carbonic Anhydrase Inhibitor Acetazoleamide on Urinary Bicarbonate Excretion

¹ From the Department of Medicine, University of Sheffield, Sheffield, England

The effects of repeated doses of the carbonic anhydrase inhibitor acetazoleamide on renal reabsorption and excretion of bicarbonate have been studied in normal persons. When administered at intervals of a few hours, acetazoleamide was found to reduce the amount of bicarbonate reabsorbed from a liter of the glomerular filtrate to a new approximately constant level. The resultant urinary excretion of bicarbonate caused a progressive reduction of plasma bicarbonate concentration and, since the glomerular filtration rate was unchanged, of the rate of bicarbonate filtration. A theoretical analysis is given of the dynamic sequence of related changes in filtration and excretion of bicarbonate which would be expected to result automatically from reduction of bicarbonate reabsorption to a new constant level. In the individuals studied the observed sequences agreed reasonably well with those predicted by the analysis, and on this basis it is concluded that the transience of the effects of acetazoleamide on urinary bicarbonate excretion may represent the operation of an automatic continuously self-limiting mechanism.

Note:
with the technical assistance of M. S. Greaves and an Appendix by D. Kerridge.