Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and Sevelamer Carbonate

Yang, Yongsheng; Mohammad, Adil; Berendt, Robert T.; Carlin, Alan S.; Khan, Mansoor A.; Faustino, Patrick J.

doi:10.1002/jps.24572

Cited by 8 publications

(4 citation statements)

References 29 publications

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“…Similarly, significant adsorption of IAA was observed with a high concentration of sevelamer carbonate (15 mg/mL). Although the adsorption of phosphorus by sevelamer carbonate was significantly greater at pH 6 than at pH 8, which was consistent with a previous study showing a higher effect of sevelamer on phosphorus adsorption in an acid condition [27,28]. We did not observe other major differences between pH 6 and pH 8 with regard to sevelamer’s adsorption of uremic toxins; indeed the difference was statistically significant but small for IAA.…”

Section: Discussionsupporting

confidence: 91%

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Bennis

Cluet

Titeca-Beauport

et al. 2019

Toxins

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High serum levels of gut-derived uremic toxins, especially p-cresyl sulfate (pCS), indoxyl sulfate (IS) and indole acetic acid (IAA), have been linked to adverse outcomes in patients with chronic kidney disease (CKD). Sevelamer carbonate could represent an interesting option to limit the elevation of gut-derived uremic toxins. The aim of the present study was to evaluate the adsorptive effect of sevelamer carbonate on different gut-derived protein-bound uremic toxins or their precursors in vitro, and its impact on the serum levels of pCS, IS and IAA in patients with CKD stage 3b/4. For the in vitro experiments, IAA, p-cresol (precursor of pCS) and indole (precursor of IS), each at a final concentration of 1 or 10 µg/mL, were incubated in centrifugal 30 kDa filter devices with 3 or 15 mg/mL sevelamer carbonate in phosphate-buffered saline at a pH adjusted to 6 or 8. Then, samples were centrifuged and free uremic toxins in the filtrates were analyzed. As a control experiment, the adsorption of phosphate was also evaluated. Additionally, patients with stage 3b/4 CKD (defined as an eGFR between 15 and 45 mL/min per 1.73 m2) were included in a multicenter, double-blind, placebo-controlled, randomized clinical trial. The participants received either placebo or sevelamer carbonate (4.8 g) three times a day for 12 weeks. The concentrations of the toxins and their precursors were measured using a validated high-performance liquid chromatography method with a diode array detector. In vitro, regardless of the pH and concentration tested, sevelamer carbonate did not show adsorption of indole and p-cresol. Conversely, with 10 µg/mL IAA, use of a high concentration of sevelamer carbonate (15 mg/mL) resulted in a significant toxin adsorption both at pH 8 (mean reduction: 26.3 ± 3.4%) and pH 6 (mean reduction: 38.7 ± 1.7%). In patients with CKD stage 3b/4, a 12-week course of treatment with sevelamer carbonate was not associated with significant decreases in serum pCS, IS and IAA levels (median difference to baseline levels: −0.12, 0.26 and −0.06 µg/mL in the sevelamer group vs. 1.97, 0.38 and 0.05 µg/mL in the placebo group, respectively). Finally, in vitro, sevelamer carbonate was capable of chelating a gut-derived uremic toxin IAA but not p-cresol and indole, the precursors of pCS and IS in the gut. In a well-designed clinical study of patients with stage 3b/4 CKD, a 12-week course of treatment with sevelamer carbonate was not associated with significant changes in the serum concentrations of pCS, IS and IAA.

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Section: Discussionsupporting

confidence: 91%

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Bennis

Cluet

Titeca-Beauport

et al. 2019

Toxins

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“…Meanwhile, Yang et al indicated that, in comparison with sevelamer carbonate, sevelamer hydrochloride can significantly reduce blood bicarbonate levels (14). Moreover, Jokihaara et al, following of nine weeks of treatment with various drugs, including sevelamer hydrochloride, showed that sevelamer hydrochloride significantly reduced blood pH and lowered the bicarbonate level (15).…”

Section: Discussionmentioning

confidence: 99%

Comparing the effect of sevelamer carbonate and sevelamer hydrochloride on plasma pH, bicarbonate and gastrointestinal complications in patients undergoing maintenance hemodialysis

Fazeli

Hajisalimi

2022

J Ren Endocrinol

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Introduction: Regular dialysis, is not able to maintain phosphorus in the normal range. Therefore, using phosphate chelators to keep serum level of phosphorus in the normal range is essential. Sevelamer is a chelator for phosphate. Objectives: The purpose of this investigation was to compare the therapeutic impact of sevelamer carbonate versus sevelamer hydrochloride on electrolytes and metabolic acidosis and gastrointestinal symptoms in a group of hemodialysis patients. Patients and Methods: In this randomized clinical trial, patients were divided into two treatment groups; sevelamer carbonate and sevelamer hydrochloride. Sevelamer carbonate and sevelamer hydrochloride were prescribed as daily 800 mg tablets three times daily with their meals. Patients were evaluated for serum calcium, phosphorus, plasma bicarbonate and pH levels after one month. Results: Around 44 patients were enrolled, of which 22 patients were treated with sevelamer hydrochloride and 22 patients in the intervention group with sevelamer carbonate. There was no significant difference between the effects of sevelamer carbonate and sevelamer hydrochloride on serum calcium and phosphorus levels at the end of the study (P>0.05). There was a significant difference between the effects of sevelamer carbonate versus sevelamer hydrochloride on plasma bicarbonate and pH levels (P=0.036 and P=0.012 respectively). In terms of gastrointestinal complications, two drugs did not differ significantly. Conclusion: To prevent acidosis, along with increasing plasma bicarbonate and blood pH in patients undergoing hemodialysis, sevelamer carbonate is better than sevelamer hydrochloride. Therefore, the administration of sevelamer hydrochloride is preferable. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20141016019554N13, https:// en.irct.ir/trial/28916, ethical code#IR.ZUMS.REC.1397.352).

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“…Inductively coupled plasma-optical emission spectrometry (ICP-OES) has additional advantages in terms detection limits and speed of analysis. The LOQ of the method were all above 0.2 mM [14]- [15].…”

Section: Introductionmentioning

confidence: 94%

In-vitro Equilibrium Phosphate Binding Study of Sevelamer Carbonate by UV-Vis Spectrophotometry

Prasaja¹,

Syabani²,

Sari³

et al. 2018

Drug Res (Stuttg)

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Sevelamer carbonate is a cross-linked polymeric amine; it is the active ingredient in Renvela tablets. US FDA provides recommendation for demonstrating bioequivalence for the development of a generic product of sevelamer carbonte using in-vitro equilibrium binding study. A simple UV-vis spectrophotometry method was developed and validated for quantification of free phosphate to determine the binding parameter constant of sevelamer. The method validation demonstrated the specificity, limit of quantification, accuracy and precision of measurements. The validated method has been successfully used to analyze samples in in-vitro equilibrium binding study for demonstrating bioequivalence.

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Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and Sevelamer Carbonate

Cited by 8 publications

References 29 publications

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Comparing the effect of sevelamer carbonate and sevelamer hydrochloride on plasma pH, bicarbonate and gastrointestinal complications in patients undergoing maintenance hemodialysis

In-vitro Equilibrium Phosphate Binding Study of Sevelamer Carbonate by UV-Vis Spectrophotometry

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