CONTEXT: Cinacalcet induces immediate changes in serum PTH levels, but the pharmacodynamic effect throughout the daily dosing interval in controlled patients is unknown. Also, in patients with reduced PTH, it is unknown what happens in the first 24 hours after withdrawal. OBJECTIVE: Our aim was to describe the effect over 48 hours of cinacalcet in hemodialysis patients with controlled secondary hyperparathyroidism. DESIGN: This was a phase 4, open-label, single-arm, single-dose, single-center clinical trial. SETTING: The study was conducted at a public hospital (Hospital Perpetuo Socorro, Alicante, Spain). PATIENTS: We included 10 patients on cinacalcet for 6 months or longer with intact PTH (iPTH) levels 100-400 pg/mL [8 men, mean age of 66 years (range 39-82 years)], chronically treated with 30 mg (n = 6), 60 mg (n = 3), or 90 mg (n = 1) of cinacalcet. INTERVENTION: A single dose (30-90 mg) was administered at baseline. MAIN OUTCOME MEASURES: iPTH (Duo Kit Scantibodies and Elecsys Roche), PTH 1-84, ionized calcium, phosphorus (P), and calcitonin were determined at baseline and at 1, 3, 6, 12, 24, and 48 hours. RESULTS: There was a significant reduction in iPTH between 1 and 6 hours, and values returned to baseline at 24 hours [maximum mean (95% confidence interval) percent change from baseline: -50%(-34; -66) at 3 hours]. A transient increase in calcitonin and a decrease in P were also observed, with no changes in calcium. At 48 hours, there was a significant increase in iPTH [+51% (26; 76)] and P. Changes in PTH were similar with the 3 determination methods. CONCLUSIONS: In hemodialysis patients with secondary hyperparathyroidism controlled by cinacalcet, a transient (1-6 hours) reduction in PTH and P and an increase in calcitonin are observed after each daily dose, with return to baseline at 24 hours. After calcimimetics discontinuation, PTH was significantly increased at 48 hours. The assay used to measure PTH does not influence relative changes induced by cinacalcet.
RCT Entities:
CONTEXT: Cinacalcet induces immediate changes in serum PTH levels, but the pharmacodynamic effect throughout the daily dosing interval in controlled patients is unknown. Also, in patients with reduced PTH, it is unknown what happens in the first 24 hours after withdrawal. OBJECTIVE: Our aim was to describe the effect over 48 hours of cinacalcet in hemodialysis patients with controlled secondary hyperparathyroidism. DESIGN: This was a phase 4, open-label, single-arm, single-dose, single-center clinical trial. SETTING: The study was conducted at a public hospital (Hospital Perpetuo Socorro, Alicante, Spain). PATIENTS: We included 10 patients on cinacalcet for 6 months or longer with intact PTH (iPTH) levels 100-400 pg/mL [8 men, mean age of 66 years (range 39-82 years)], chronically treated with 30 mg (n = 6), 60 mg (n = 3), or 90 mg (n = 1) of cinacalcet. INTERVENTION: A single dose (30-90 mg) was administered at baseline. MAIN OUTCOME MEASURES: iPTH (Duo Kit Scantibodies and Elecsys Roche), PTH 1-84, ionizedcalcium, phosphorus (P), and calcitonin were determined at baseline and at 1, 3, 6, 12, 24, and 48 hours. RESULTS: There was a significant reduction in iPTH between 1 and 6 hours, and values returned to baseline at 24 hours [maximum mean (95% confidence interval) percent change from baseline: -50%(-34; -66) at 3 hours]. A transient increase in calcitonin and a decrease in P were also observed, with no changes in calcium. At 48 hours, there was a significant increase in iPTH [+51% (26; 76)] and P. Changes in PTH were similar with the 3 determination methods. CONCLUSIONS: In hemodialysis patients with secondary hyperparathyroidism controlled by cinacalcet, a transient (1-6 hours) reduction in PTH and P and an increase in calcitonin are observed after each daily dose, with return to baseline at 24 hours. After calcimimetics discontinuation, PTH was significantly increased at 48 hours. The assay used to measure PTH does not influence relative changes induced by cinacalcet.
Authors: A E Cook; S N Mistry; K J Gregory; S G B Furness; P M Sexton; P J Scammells; A D Conigrave; A Christopoulos; K Leach Journal: Br J Pharmacol Date: 2014-12-01 Impact factor: 8.739
Authors: Geert J Behets; Goce Spasovski; Lulu R Sterling; William G Goodman; David M Spiegel; Marc E De Broe; Patrick C D'Haese Journal: Kidney Int Date: 2014-10-22 Impact factor: 10.612