title: 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.
abstract: 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.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. ohashi-n@hama-med.ac.jp
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Uematsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagashima
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Kanamaru
authors.forename: Akashi
authors.initials: A
authors.lastname: Togawa
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
authors.forename: Shozo
authors.initials: S
authors.lastname: Koshikawa
mesh_terms: 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
chemical_list: D009281:Naphthalenes; D010281:Parathyroid Hormone; D002118:Calcium; D000069449:Cinacalcet