Abstract
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 (2°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 2°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 2°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 2°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 2°HPT or the basal plasma Ca2+ or phosphate levels. In rats with severe 2°HPT, the minimum plasma PTH level after NPS R-568 was greater than the basal level in mild 2°HPT. Thus, NPS R-568 is equally effective in suppressing plasma PTH and Ca2+ levels in rats with mild or severe renal or nutritional 2°HPT.
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Fox, J., Lowe, S.H., Conklin, R.L. et al. The calcimimetic NPS R-568 decreases plasma PTH in rats with mild and severe renal or dietary secondary hyperparathyroidism. Endocr 10, 97–103 (1999). https://doi.org/10.1385/ENDO:10:2:97
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DOI: https://doi.org/10.1385/ENDO:10:2:97