A CALCIMIMETIC AGENT ACUTELY SUPPRESSES PARATHYROID-HORMONE LEVELS INPATIENTS WITH CHRONIC-RENAL-FAILURE - RAPID COMMUNICATION

The control of hyperparathyroidism in patients with chronic renal fail ure continues to be a problem, particularly when parathyroid hormone ( PTH) suppression becomes refractory to calcitriol activation of parath yroid cell 1,25-dihydroxyvitamin D receptors. To evaluate whether para thyroid cell calcium receptor activation may be useful in suppressing PTH levels, we tested the safety and effectiveness of a novel calcimim etic agent in dialysis patients with hyperparathyroidism. In a prospec tive, dose finding study, the calcimimetic agent, NPS R-568, was admin istered orally to seven patients at the start of a hemodialysis sessio n and again 24 hours later. Plasma PTH, calcitonin and ionized calcium levels were measured over a 48 hour period and patients were observed for adverse events. Plasma PTH levels fell abruptly in all patients a fter a single dose of the compound, with the maximum suppression occur ring within one to two hours after its administration. Following the a dministration of low doses (40 or 80 mg), the suppressed PTH levels ro se to baseline values over 48 hours, whereas in patients who received high doses (120 or 200 mg) the mean PTH level remained 51% below basel ine. Plasma calcitonin increased after the administration of both low and high doses (peak effect within 4 to 6 hr), with levels always retu rning to baseline by 48 hours. There were no episodes of hypocalcemia and no adverse effects were reported. We conclude that the activation of parathyroid cell calcium receptors by a novel calcimimetic compound is safe and effective in acutely suppressing PTH secretion in dialysi s patients with hyperparathyroidism. Whether concomitant stimulation o f calcitonin secretion will provide added beneficial effects on bone r emodeling remains to be determined in long-term studies.