Clinical Pharmacokinetic and Pharmacodynamic Profile of Cinacalcet
Abstract
The purpose of this letter is to explain clinical pharmacokinetic, pharmacodynamic profile and indication of cinacalcet therapy particularly in chronic kidney disease. Chronic kidney disease and progressive renal failure are associated with phosphate retention and impaired formation of active vitamin D, or calcitriol (1α-25-dihydroxyvitamin D), leading to hypocalcemia, increased secretion of parathyroid hormone, and, eventually, hyperplasia of the parathyroid gland. Secondary hyperparathyroidism is frequent and progresses over time in patients with chronic kidney disease. It develops as a result of disturbance in parathyroid hormone, calcium, phosphate, and vitamin D homeostasis. Risk factors are mainly hyperphosphatemia and increased calcium-phosphate products1. The related mineral and bone disorders are early onset, common and serious complications because of their significant impact on morbidity and mortality due to skeletal (renal osteodystrophy, loss of bone mineral density, bone pain, and fractures) and extra skeletal manifestations particularly cardiovascular manifestations2,3. Conventional treatment with a calcium supplement, phosphate binders and active vitamin D derivatives lead in part to amelioration of secondary hyperparathyroidism, but are simultaneously associated with unacceptable side-effects, including hypercalcemia, hyperphosphatemia, and increased calcium-phosphate products1
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