The Calcimimetic NPS R-568 Decreases Plasma PTH in Rats with Mild and Severe Renal or Dietary Secondary Hyperparathyroidism

NPS R-568 is a Ca2+ receptor agonist ("calcimimetic") compound that reduces circulating parathyroid hormone (PTH) levels in rats and humans with mild secondary hyperparathyroidism (secondary HPT) resulting from chronic renal insufficiency (CRI). These studies extend those observations to show that NPS R-568 is equally effective in decreasing plasma PTH and Ca2+ levels in rats with mild or severe secondary HPT, resulting either from CRI or from dietary calcium deficiency. Male rats were 5/6 nephrectomized and fed either normal chow or a high-phosphorus diet; other normal rats were fed a low-calcium diet. When secondary HPT had developed, NPS R-568 was administered and blood samples were collected for up to 6 h. PTH levels decreased to a minimum level within 30 min in both CRI and calcium deficiency models of secondary HPT. PTH and Ca2+ levels remained significantly depressed for >3 h after dosing. The percentage decrease in PTH levels was unaffected by the severity of secondary HPT or the basal plasma Ca2+ or phosphate levels. In rats with severe secondary HPT, the minimum plasma PTH level after NPS R-568 was greater than the basal level in mild secondary HPT. Thus, NPS R-568 is equally effective in suppressing plasma PTH and Ca2+ levels in rats with mild or severe renal or nutritional secondary HPT.