In an attempt to explain the
triamterene stone
diathesis, we studied the excretion and solubility of
triamterene, 1, and its metabolite, the
sulfate ester of the hydroxy derivative of
triamterene, 3. The urinary excretion pattern and metabolism in stone formers was the same as in other chronic users of
triamterene or healthy volunteers. The solubility of
triamterene in urine was approximately one-half of its solubility in
buffer solution, whereas the
sulfate ester, 3, was nearly twice as soluble in urine as in the
buffer solution. In the majority of the subjects studied, we found concentrations of 3 which approached or exceeded apparent solubility limits in urine. This was not true for
triamterene where most measured urine concentrations were less than the apparent solubility as determined by equilibration. Alteration in the metabolism of
triamterene is probably not a causative factor for
triamterene nephrolithiasis. The saturation of urine with
triamterene and especially with the
sulfate ester, 3, may be related to stone formation, but other physical factors play a role in determining the relative amounts of
drug found in
calculus material.