Calcelar 25 Mechanism of Action

Pharmacology: Cinacalcet exerts its effects by acting on calcium receptors on the surface of parathyroid cells. Calcium receptors control synthesis of PTH and proliferation of parathyroid cells, as well as secretion of PTH. The drug decreases the serum PTH level by acting on calcium receptors and mainly suppressing PTH secretion. Furthermore, in repeated-dose administration, its effect of suppressing proliferation of parathyroid cells is also considered to contribute to a decrease in serum PTH level.
Actions/Effects: Inhibition of PTH Secretion (in vitro): Cinacalcet was shown to inhibit PTH secretion from bovine parathyroid cells and human parathyroid cells dose-dependently.
Suppression of proliferation of parathyroid cells: Following repeated-dose oral administration to partially nephrectomized rats, Cinacalcet was shown to inhibit proliferation of parathyroid cells and thereby suppress progression of parathyroid hyperplasia.
Decrease in the serum PTH and calcium levels: Following single-dose oral administration to normal rats and partially nephrectomized rats, Cinacalcet was shown to decrease the serum PTH and calcium levels dose-dependently.
Suppression of bone disorder: In patients with secondary hyperthyroidism, bone disorder develops due to increased serum PTH. Following repeated-dose oral administration to partially nephrectomized rats, Cinacalcet was shown to suppress symptoms associated with bone disorder due to increased serum PTH, such as marrow fibrosis, cortical osteoporosis, and decreases in cortical bone density and bone strength.
Pharmacokinetics: Absorption: For single oral administration of Cinacalcet at dose of 25, 50 and 100 mg during fasting condition, the plasma concentration of Cinacalcet increased dose dependently both on the non-dialysis and dialysis day for hemodialysis patients with secondary hyperthyroidism.
After multiple oral administration of Cinacalcet at hemodialysis patients with secondary hyperthyroidism, no tendency of increasing or decreasing over time on the plasma trough concentration and plasma concentration have reached a steady state following repeated-dose administration.
The effect of food on the pharmacokinetics of Cinacalcet is small.
Distribution: Protein-binding of Cinacalcet (25-100 ng/mL) in human plasma is 96.67-97.67% in males and 94.33-97.67% in females, respectively, and there is no sex difference.
Metabolism: Cinacalcet is extensively metabolized via N-dealkylation and oxidation of the naphthalene ring.
Elimination: Cinacalcet is excreted mainly in urine as metabolites.
Special populations: Renal and Hepatic impairment: Protein-binding is similar among normal, hepatic and renal impairment population which is 94.7-97.1% for normal and hepatic impairment population, and 92.7-95.1% for normal and renal impairment population, respectively. Cinacalcet is considered to be bound to albumin and shown to have a high affinity to the site II.