THE EFFECT OF PTH ANTAGONIST BIM-44002 ON SERUM-CALCIUM AND PTH LEVELS IN HYPERCALCEMIC HYPERPARATHYROID PATIENTS

BIM-44002, a pure competitive antagonist of parathyroid hormone (PTH), has a high affinity for the PTH/PTHrP receptor in vitro, and can comp letely inhibit the actions of a PTH agonist in rats in vivo. Toxicolog y studies in rats and dogs showed BIM-44002 to be devoid of any advers e effects. Therefore we undertook an investigation to evaluate the pot ential utility of BIM-44002 in lowering elevated serum calcium in thre e patients with primary hyperparathyroidism. BIM-44002 was administere d by continuous intravenous infusion at dosages of 100 mu g/hour (370 nmol/hour) for 12 hours, followed by 200 mu g/hour for 12 hours, follo wed by 400 mu g/hour for 12 hours. Vital signs and serum ionized and t otal calcium were monitored hourly and for 3 hours after cessation of the infusion. Blood for PTH determinations was obtained at the same ti me points. Serum calcium and PTH did not change during and after the i nfusion of the antagonist. No subject experienced any adverse reaction s to the infusion of the antagonist. We conclude that although the PTH antagonist BIM-44002 was effective both in vitro and in vivo in anima ls, and it was safe in humans, it was not able to lower serum calcium in patients with hyperparathyroidism. Possible reasons for lack of cli nical efficacy are discussed.