Effect of Sulfonamides on the Hypercalcemic Response to Vitamin D

Summary

Parathyroidectomized rats were fasted for twenty-four hours then treated with 10⁶ units/kg of vitamin D₃. Twelve hours later the animals were bilaterally nephrectomized and treated with either the appropriate control solution or one of the following: acetazolamide, methazolamide, ethoxzolamide or CL 13,850. Animals treated with the vitamin exhibited an increase in plasma calcium of approximately 5 mg/dl. This response was antagonized by treatment with acetazolamide, methazolamide or ethoxzolamide. These agents are all sulfonamide inhibitors of carbonic anhydrase. CL 13,850, a structural analog of acetazolamide that is devoid of enzyme inhibitory activity, was also devoid of inhibitory activity with respect to the hypercalcemic response to vitamin D₃. Acetazol-amide inhibited the response to the vitamin at doses yielding ultrafiltrable plasma drug concentrations of approximately 10^-5 to 10^-4M. The hypercalcemic response observed following the administration of the active metabolite of vitamin D₃ (1,25-dihydroxyvitamin D₃) was attenuated by treatment with acetazolamide.

Key-Words:

Vitamin D ₃ - 1,25-Dihydroxycholecalciferol - Hypercalcemia - Acetazolamide - Carbonic Anhydrase