Assessment of phosphate binding by sevelamer carbonate powder for oral suspension mixed in foods.

This study investigated mixing sevelamer carbonate powder with foods and beverages other than water. Food samples, including applesauce, oatmeal, chicken, protein powder, scrambled eggs, ginger ale, and diet ginger ale, were subjected to an in vitro assay, and the difference in the amount of phosphate bound between samples pre-exposed to foods and samples where the drug was exposed to foods concurrently was determined Under these assay conditions, pre-exposure to sevelamer carbonate powder had no effect on the ability to bind phosphate. Clinical testing is needed to further evaluate this finding.

Bile acid salt binding with colesevelam HCl is not affected by suspension in common beverages.

It has been previously reported that anions in common beverages may bind to bile acid sequestrants (BAS), reducing their capacity for binding bile acid salts. This study examined the ability of the novel BAS colesevelam hydrochloride (HCl), in vitro, to bind bile acid sodium salts following suspension in common beverages. Equilibrium binding was evaluated under conditions of constant time and varying concentrations of bile acid salts in simulated intestinal fluid (SIF). A stock solution of sodium salts of glycochenodeoxycholic acid (GCDC), taurodeoxycholic acid (TDC), and glycocholic acid (GC), was added to each prepared sample of colesevelam HCl. Bile acid salt binding was calculated by high-performance liquid chromatography (HPLC) analysis. Kinetics experiments were conducted using constant initial bile acid salt concentrations and varying binding times. The affinity, capacity, and kinetics of colesevelam HCl binding for GCDC, TDC, and GC were not significantly altered after suspension in water, carbonated water, Coca-Cola, Sprite, grape juice, orange juice, tomato juice, or Gatorade. The amount of bile acid sodium salt bound as a function of time was unchanged by pretreatment with any beverage tested. The in vitro binding characteristics of colesevelam HCl are unchanged by suspension in common beverages.

Novel dosage forms and regimens for sevelamer-based phosphate binders.

Sevelamer, a nonabsorbed, calcium- and metal-free dietary phosphate binder, consists of a polyallylamine polymer backbone with a cationic charge that shows a high capacity for binding anionically charged compounds such as phosphate. The currently licensed form of sevelamer, Renagel, exists as sevelamer hydrochloride, which disassociates in the acidic environment of the stomach and early gastrointestinal tract, exchanging the chloride ions attached to the polymer backbone for phosphate ions. The resulting absorption of these chloride ions has been reported to be accompanied by a reduction in serum levels of bicarbonate in some patients. To minimize the possibility of this effect, a new salt form of sevelamer has been developed in which carbonate replaces the chloride counter ion, thereby providing a source of buffer. The majority of phosphate binders exist only in tablet form and are dosed three times per day with meals. Genzyme has developed sevelamer carbonate in tablet form and also as a powder formulation that can be taken after mixing with water. This allows for an alternate and potentially more palatable way of dosing. Preliminary data exist suggesting that once daily dosing with sevelamer hydrochloride tablets provides similar phosphate control to three times daily dosing. By providing novel dosage forms and regimens for sevelamer-based phosphate binders, Genzyme will be providing patients and health care providers additional choices and flexibility in controlling phosphorus levels in chronic kidney disease. This should translate to increased compliance and improved rates of phosphate control.

Determination of the binding parameter constants of Renagel capsules and tablets at pH 7 by high performance capillary electrophoresis.

Sevelamer hydrochloride is a cross-linked polymeric amine; it is the active ingredient in Renagel capsules and tablets. Sevelamer hydrochloride is indicated for the control of hyperphosphatemia in patients with end-stage renal disease (ESRD). The binding parameter constants of sevelamer hydrochloride were determined using high performance capillary electrophoresis (HPCE) and the Langmuir approximation for three different dosage forms at pH 7.0. The three dosage forms were Renagel 403 mg capsules, Renagel 400 mg tablets and Renagel 800 mg tablets. The results demonstrate the in vitro bioequivalence of all three dosage forms at pH 7.0. These results are in very good agreement with previously published results obtained by ion chromatography.

Determination of the binding parameter constants of Renagel capsules and tablets utilizing the Langmuir approximation at various pH by ion chromatography.

Sevelamer hydrochloride is a cross-linked polymeric amine; it is the active ingredient in Renagel capsules and tablets. Sevelamer hydrochloride is indicated for the control of hyperphosphatemia in patients with end-stage renal disease. The binding parameter constants of sevelamer hydrochloride were determined using the Langmuir approximation for three different dosage forms at pH 4.0, 5.5 and 7.0. The three dosage forms were Renagel 403 mg capsules, Renagel 400 mg tablets and Renagel 800 mg tablets. The results demonstrate the equivalency of all three dosage forms at each pH. The results also demonstrate a shift in the binding mechanism from pH 4.0 to 7.0.

Bile acid binding to sevelamer HCl.

BACKGROUND: Clinical studies have shown sevelamer HCl (Renagel) to be effective for the reduction of serum phosphate in hemodialysis patients. These studies also consistently have demonstrated a significant reduction of low-density lipoprotein (LDL) cholesterol following treatment with sevelamer. METHODS: Equilibrium binding of bile acids and oleic acid was determined by incubating sevelamer with ligand containing buffer. Aliquots of the solution were filtered and the free ligand concentrations quantitated by high-pressure liquid chromatography (HPLC). Flow kinetics were determined using a cylindrical flow cell containing trapped sevelamer. Bile acid and oleic acid were pumped through the stirred cell in a manner designed to mimic the in vivo situation. Binding was monitored by HPLC. RESULTS: Sevelamer binds bile acids cooperatively and with high capacity. At low binding densities, the presence of the more hydrophobic bile acids enhances the binding of the less hydrophobic bile acids, and the presence of oleic acid enhances the binding of all bile acids. At saturating oleic acid concentrations, the bile acid binding capacity of sevelamer is reduced by only a factor of two. Moreover, the presence of oleic acid dramatically diminishes the release rate of bile acids from sevelamer. CONCLUSIONS: The favorable bile acid binding characteristics of sevelamer provide a compelling explanation for its ability to lower LDL cholesterol in hemodialysis patients and in healthy volunteers.