A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism

Background. The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH) levels in hemodialysis patients with mild secondary hyperparathyroidi sm, but its efficacy in those with more severe secondary hyperparathyroidis m has not been studied. Methods. Twenty-one patients undergoing hemodialysis three times per week w ith 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 o f 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 t he first day of treatment did not change in those given placebo. In contras t, 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 pre treatment 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 t han 50% two hours after drug administration. Predose PTH levels declined pr ogressively over the first nine days of treatment with R-568 and remained b elow pretreatment levels for the duration of study. Serum total and blood i onized calcium concentrations decreased from pretreatment levels in patient s 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 hypoc alcemia, whereas three completed treatment after the dose of R-568 was redu ced. Conclusions. The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage r enal disease.