Sefos Mechanism of Action

Pharmacology: Pharmacodynamics: Patients with chronic kidney disease retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcifications. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 55 mg²/dL² there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency. An increase in parathyroid hormone (PTH) level is characteristics of patients with chronic kidney disease. Increased level of PTH can lead to osteitis fibrosa. A decrease in serum phosphorus may decrease serum PTH levels.
Treatment of hyperphosphatemia includes reduction of dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders and removal of phosphate with dialysis. Sevelamer Carbonate taken with meals has been shown to decrease serum phosphorus concentration in patients with chronic kidney disease who are on hemodialysis. In vitro studies have shown that the capsule and tablet formulations bind phosphate to a similar extent.
Sevelamer Carbonate treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels.
Mode of Action/Pharmacodynamic Characteristics Mechanism of action: Sevelamer Carbonate contains Sevelamer hydrochloride, a non-absorbed phosphate binding poly (allylamine hydrochloride) polymer, free of metal and calcium. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a partially protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the dietary tract, Sevelamer hydrochloride lowers the phosphate concentration in the serum. In clinical trials, Sevelamer hydrochloride has been shown to be effective in reducing serum phosphorus in patients receiving hemodialysis or peritoneal dialysis.
Sevelamer hydrochloride decreases the incidence of hypercalcemic episodes as compared to patients using calcium based phosphate binders alone. The effects on phosphate and calcium were proven to be maintained throughout a study with one year follow-up.
Sevelamer hydrochloride has been shown to bind bile acids in vitro and in vivo in experimental animal models. Bile acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. In clinical trials, both the mean total and LDL cholesterol is declined by 15 - 31%. This effect is observed after 2 weeks and is maintained with long-term treatment. Triglycerides, HDL cholesterol and albumin did not change.
In the clinical studies in hemodialysis patients, Sevelamer hydrochloride alone did not have a consistent and clinically significant effect on serum intact parathyroid hormone (iPTH). In patients with secondary hyperparathyroidism, Sevelamer Carbonate should be used within the context of a multiple therapeutic approach, which could include calcium supplements, and 1, 25-dihydroxyvitamin D3 or one of its analogues to lower the intact parathyroid hormone (iPTH) levels.