Hypocalcaemic Effect of WR-2721, S-2 (3-Aminopropylamino) Ethyl-phosphorothioic Acid in an Anuric Haemodialysis Patient

The radio- and chemoprotective agent, S-2 (3-aminopropylamino)ethyl-phosphorothioic acid (WR 2721) has been reported to lowerhypercalcaemia in patients with cancer, probably by increasedrenal calcium excretion and decreased parathyroid hormone (PTH)secretion and bone calcium resorption. The present study reportsthe first clinical use of WR-2721 in an anuric haemodialysispatient with severe secondary hyperparathyroidism. The drugwas administered intravenously at different doses, i.e. 150,300, and 500 mg/m². The infusion was followed by a strikingdecrease of plasma immunoreactive (i) PTH within 30 min. Thenadir of the iPTH decrease was reached at 60 min and was followedby a steady return to previous values. Serum ionised calciumdecreased more progressively from 1.55 mmol/l initially to 1.30mmol/l at 4 h after the 300-mg dose, remained at that levelat 24 h, but rose again to pre-infusion values after 48 h. Theextent and duration of the decrease in plasma iPTH and ionisedcalcium were dose-dependent. The circulating iPTH at 24 h wasinversely related to the corresponding plasma ionised calciumconcentration and had risen above preinfusion values at thattime. Plasma concentrations of three other hormones, i.e. renin,insulin, and prolactin, were not affected by the administrationof WR-2721. In conclusion, WR-2721 can induce a decrease in serum ionisedcalcium in the absence of any excretory kidney function. Therapid effect of the drug on circulating iPTH supports the notionof an interference with PTH secretion or catabolism.