Biological effects of the enhanced excretion of zinc after calcium diethylenetriaminepentaacetate chelation therapy.

An enhanced, uncompensated excretion of zinc may be responsible for unwanted side-effects that could develop after prolonged chelation therapy with calcium diethylenetriaminepentaacetate (Ca-DTPA). As a preliminary means of defining "potential toxicity" within this hypothesis, the "normal" concentration range of Zn++ excreted in the urine of three adult female baboons was measured on a daily basis; changes in urinary Zn++ excretion were then quantitated as a function of the injection time and dose of the chelating agent Na3(Ca-DTPA) originally administered to enhance the excretion of 241Am from the body. In addition, the inhibitory action of the chelator compound on the activity of a specific metalloenzyme system, erythrocytic aminolevulinic acid dehydratase (ALAD), which requires Zn++ as a co-factor, has been determined as a measure of a specific biological effect. It was found that whenever the concentration of Zn++ in urine was above 2 mug/ml (or greater than approximately four times the "normal" urinary excretion level), the activity of ALAD dropped below 250 nmol PBG/ml RBC/hr or approximately one-half the mean "normal" activity value for this primate species.