The calcimimetic agent KRN 1493 lowers plasma parathyroid hormone and ionized calcium concentrations in patients with chronic renal failure on haemodialysis both on the day of haemodialysis and on the day without haemodialysis.
OBJECTIVE
Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in patients with secondary hyperparathyroidism; however, hypercalcaemia, hyperphosphataemia, or both, often develop. Calcimimetic agents, employed in alternative therapeutic approaches, directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands.


METHODS
In this study, patients were given orally 25, 50, and 100 mg doses of the calcimimetic agent KRN 1493 each on two occasions, on the day of haemodialysis and on the day without haemodialysis.


RESULTS
In the pharmacokinetic results, because the clearance of KRN 1493 by haemodialysis was much smaller than the systemic clearance, the influence of haemodialysis was not remarkable. In the pharmacodynamic study, on both the days with or without haemodialysis, plasma PTH concentrations decreased in a dose-dependent manner. Serum calcium concentrations decreased in association with the decrease in plasma PTH concentrations. Mild dose-dependent adverse effects (mainly nausea) were seen after the administration of KRN 1493 on both the day of haemodialysis and the day without haemodialysis.


CONCLUSIONS
We conclude that the pharmacokinetics of KRN 1493 after a single administration were similar on the day of haemodialysis and the day without haemodialysis. KRN 1493 is safe and effective in suppressing PTH secretion and serum calcium concentrations on the day of haemodialysis and on the day without haemodialysis in patients with secondary hyperparathyroidism.
Ohashi
Naro
N
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. ohashi-n@hama-med.ac.jp
Uematsu
Toshihiko
T
Nagashima
Satoru
S
Kanamaru
Mitsutaka
M
Togawa
Akashi
A
Hishida
Akira
A
Uchida
Eiji
E
Akizawa
Tadao
T
Koshikawa
Shozo
S
D000284:Administration, Oral; D002118:Calcium / Q000097:blood*; D000069449:Cinacalcet; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000097:blood*; D006435:Renal Dialysis
D009281:Naphthalenes; D010281:Parathyroid Hormone; D002118:Calcium; D000069449:Cinacalcet