title: A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism.
abstract: BACKGROUND
  The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH) levels in hemodialysis patients with mild secondary hyperparathyroidism, but its efficacy in those with more severe secondary hyperparathyroidism has not been studied.
  
  
  METHODS
  Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were randomly assigned to 15 days of treatment with either 100 mg of R-568 (N = 16) or placebo (N = 5). Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1, 2, 3, 5, 8, 11, 12, and 15.
  
  
  RESULTS
  Pretreatment PTH levels were 599 +/- 105 (mean +/- SE) and 600 +/- 90 pg/mL in subjects given R-568 or placebo, respectively, and values on the first day of treatment did not change in those given placebo. In contrast, PTH levels fell by 66 +/- 5%, 78 +/- 3%, and 70 +/- 3% at one, two, and four hours, respectively, after initial doses of R-568, remaining below pretreatment values for 24 hours. Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo. Despite lower ionized calcium concentrations on both the second and third days of treatment, predose PTH levels were 422 +/- 70 and 443 +/- 105 pg/mL, respectively, in patients given R-568, and values fell each day by more than 50% two hours after drug administration. Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study. Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568, whereas values were unchanged in those given placebo. Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568; five patients withdrew from study after developing symptoms of hypocalcemia, whereas three completed treatment after the dose of R-568 was reduced.
  
  
  CONCLUSIONS
  The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease.
authors.affiliation: Division of Nephrology, Department of Medicine, UCLA School of Medicine, Los Angeles 90095, USA. wgoodman@ucla.edu
authors.forename: W G
authors.initials: WG
authors.lastname: Goodman
authors.forename: J M
authors.initials: JM
authors.lastname: Frazao
authors.forename: D A
authors.initials: DA
authors.lastname: Goodkin
authors.forename: S A
authors.initials: SA
authors.lastname: Turner
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: J W
authors.initials: JW
authors.lastname: Coburn
mesh_terms: D000328:Adult; D000814:Aniline Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D019540:Area Under Curve; D002118:Calcium / Q000819:agonists* / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D006996:Hypocalcemia / Q000139:chemically induced; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010627:Phenethylamines; D011437:Propylamines
chemical_list: D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010281:Parathyroid Hormone; D010627:Phenethylamines; D011437:Propylamines; D002118:Calcium