ferric-oxide--saccharated and lanthanum-carbonate

Hyperphosphatemia is common in chronic kidney disease (CKD) and is treated by dietary measures, dialysis techniques and/or phosphate binders. For the present review PubMed was searched for new publications on phosphate binders appearing between January 2010 and October 2015. This review summarizes the latest information on non-pharmacological measures and their problems in lowering phosphate in CKD patients, effects of phosphate binders on morbidity and mortality, adherence to phosphate binder therapy as well as new information on specific aspects of the various phosphate binders on the market: calcium acetate, calcium carbonate, magnesium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, aluminum-containing phosphate binders, and new compounds in development. The review also briefly covers the emerging field of drugs targeting intestinal phosphate transporters.

Topics: Drug Combinations; Ferric Compounds; Humans; Hyperphosphatemia; Lanthanum; Phosphates; Polyamines; Renal Insufficiency, Chronic; Sevelamer; Sucrose

Hyperphosphatemia is a frequent complication of chronic kidney disease and is associated with increased mortality. Despite side effects, risk of accumulation and high costs, phosphate binders (PBs) have become the crucial cornerstone of therapy. The iron-containing PB sucroferric oxyhydroxide (SO) and ferric citrate hydrate (FCH) have entered the market and other candidates are prior market entry.. A literature search was performed using MEDLINE and EMBASE databases to identify references on iron-containing PB with particular regard to efficacy, safety and potential benefits. Additional hand searches were conducted along with a full-text review of any citation that appeared relevant.. On the highly competitive market, where the 'ideal' PB is still unknown, novel substances that offer clear benefits over available drugs are desired. Although SO and FCH showed similar efficacy and safety compared to sevelamer, head-to-head studies with lanthanum carbonate are absent. Clinical 1-year data in a limited patient cohort suggested improved adherence for SO and a large randomized controlled trial showed significant reduction in hospitalizations and costs for FCH. Additional large randomized controlled trials have now to prove these possible advantages. Cost-effectiveness in comparison to other PB and the exclusion of significant harms under long-term treatment will determine the future use of both drugs.

Topics: Animals; Carbonates; Clinical Trials as Topic; Drug Combinations; Ferric Compounds; Humans; Hyperphosphatemia; Iron; Lanthanum; Magnesium; Phosphates; Renal Insufficiency, Chronic; Sevelamer; Starch; Sucrose

In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges.. We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment.. The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1;. Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis.. Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.

Topics: Adult; Aged; Calcinosis; Coronary Artery Disease; Disease Progression; Drug Combinations; Female; Ferric Compounds; Humans; Hyperphosphatemia; Lanthanum; Male; Middle Aged; Phosphates; Renal Dialysis; Sequestering Agents; Sucrose; Young Adult

Hyperphosphataemia is associated with increased mortality and morbidity in end stage renal disease. Despite phosphate binder therapy, a large proportion of patients do not reach the treatment target. In five contemporary binders we explored the influence of pH and phosphate concentration on phosphate binding. This interaction could be of relevance in clinical practice.. Phosphate binding was quantified in vitro in 25 mL of purified water containing phosphate concentrations of 10, 15 and 20 mM and baseline pH values of 3.0 or 6.0, with a binder over 6 h. Lanthanum carbonate, calcium acetate/magnesium carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide, 67 mg of each, were used. The experiments were performed in duplicate. The primary outcome was the difference in the amount of bound phosphate for each binder after 6 h in solutions at two different pH values. Secondary outcomes were the influence of phosphate concentration on phosphate binding, next to binding patterns and phosphate binder saturation.. In this specific in vitro setting, lanthanum carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide bound more phosphate in the solution with baseline pH of 3.0. Differences however were small except for lanthanum carbonate. Calcium acetate/magnesium carbonate was most effective in a solution with baseline pH of 6.0. All phosphate binders bound more phosphate in solutions with higher concentrations of phosphate. Sevelamer carbonate, calcium acetate/magnesium carbonate and sucroferric oxyhydroxide bound most phosphate in the first hour and reached maximum binding capacity in less than 6 h.

Topics: Acetates; Calcium Carbonate; Calcium Compounds; Chelating Agents; Drug Combinations; Ferric Compounds; Hydrogen-Ion Concentration; Kinetics; Lanthanum; Magnesium; Phosphates; Sevelamer; Sucrose

Most patients undergoing dialysis are required to take many phosphate binder pills to control hyperphosphatemia. Phosphate binders prescribed in Japan are classified into two types: metal-based binders (Ca carbonate, lanthanum carbonate, ferric citrate hydrate, and sucroferric oxyhydroxide) and chemically synthesized polymers (sevelamer hydrochloride and bixalomer). The raw materials of metal-based phosphate binders are natural ores; thus, such binders may contain several other metallic elements. We measured the elemental contents in six metal-based phosphate binders using an inductively coupled plasma mass - spectrometry (ICP-MS) method. As a result, despite being in small amounts, ore-derived phosphate binders contained various elements besides their active ingredient metals: Na, Mg, P, Mn, Fe, Sr, Y, Ba, La, Nd, and Pb in three Ca-based products; Mg, P, Se, Ce, and Gd in one La-based product; and Na, Mg, Al, P, Ca, Ti, Cr, Mn, Co, Ni, Ge, Ba, and La in two Fe-based products. These elements are considered to have originated from pharmaceutical bulk and from pharmaceutical additives. It is unlikely these elements are immediately harmful to patients. However, it should be emphasized that patients undergoing dialysis do not have a urinary excretion route and are administered many phosphate binder pills every day over a long period of time. In the future, pharmaceutical companies may have to disclose standard amounts and/or analytical values regarding the type and quantity of metallic elements in the final formulation or pharmaceutical bulk derived from natural ores.

Topics: Calcium Carbonate; Chelating Agents; Drug Combinations; Ferric Compounds; Japan; Lanthanum; Metals; Phosphates; Polyamines; Sevelamer; Spectrophotometry, Atomic; Sucrose

The phosphate binding capacity of PA21, a novel phosphate binder, was compared with those of other phosphate binders in vitro and in vivo.. 1) For in vitro studies, PA21, sevelamer hydrochloride, lanthanum carbonate hydrate, calcium carbonate, and ferric citrate hydrate were incubated with a phosphate solution at 37°C for 2 h. Phosphate binding capacity was assessed at simulated gastrointestinal tract pH levels of 2, 5, and 8 for estimation of clinical effects, and the quantity of phosphate adsorbed by each phosphate binder was determined. 2) For in vivo studies, rats were orally administered various phosphate binders after the oral administration of phosphate solution (100 mg/kg) adjusted to pH 2, 5, or 8, and the effects of PA21 and other phosphate binders on the serum phosphorus level of the rats were investigated.. 1) The in vitro studies revealed that PA21 and sevelamer hydrochloride adsorbed phosphate better at all tested pH levels than lanthanum carbonate hydrate, calcium carbonate, and ferric citrate hydrate, and PA21 showed the most potent phosphate binding capacity among the tested compounds. 2) The in vivo studies showed that PA21 dose-dependently inhibited the increase in the serum phosphorus level after the administration of phosphate solution and no difference in the extent of inhibition by PA21 was observed at the different pH levels (in contrast to other phosphate binders).. These results indicated that PA21 has a phosphate binding capacity over the entire pH range of the GI tract.

Topics: Administration, Oral; Animals; Calcium Carbonate; Chelating Agents; Drug Combinations; Ferric Compounds; Hyperphosphatemia; Lanthanum; Male; Phosphates; Rats; Rats, Sprague-Dawley; Sevelamer; Sucrose

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Topics: Animals; Body Weight; Disease Models, Animal; Drug Combinations; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Kidney Failure, Chronic; Lanthanum; Male; Mortality; Phosphates; Rats, Wistar; Sevelamer; Sucrose; Vascular Calcification