Abstract
BackgroundThe novel iron-based phosphate binder sucroferric oxyhydroxide is being investigated for the treatment of hyperphosphatemia. Patients with chronic kidney disease often have multiple comorbidities that may necessitate the daily use of several types of medication. Therefore, the potential pharmacokinetic drug–drug interactions between sucroferric oxyhydroxide and selected drugs commonly taken by dialysis patients were investigated.MethodsFive Phase I, single-center, open-label, randomized, three-period crossover studies in healthy volunteers investigated the effect of a single dose of sucroferric oxyhydroxide 1 g (based on iron content) on the pharmacokinetics of losartan 100 mg, furosemide 40 mg, omeprazole 40 mg, digoxin 0.5 mg and warfarin 10 mg. Pharmacokinetic parameters [including area under the plasma concentration–time curve (AUC) from time 0 extrapolated to infinite time (AUC0–∞) and from 0 to 24 h (AUC0–24)] for these drugs were determined: alone in the presence of food; with sucroferric oxyhydroxide in the presence of food; 2 h after food and sucroferric oxyhydroxide administration.ResultsSystemic exposure based on AUC0–∞ for all drugs, and AUC0–24 for all drugs except omeprazole (for which AUC 0–8 h was measured), was unaffected to a clinically significant extent by the presence of sucroferric oxyhydroxide, irrespective of whether sucroferric oxyhydroxide was administered with the drug or 2 h earlier.ConclusionsThere is a low risk of drug–drug interactions between sucroferric oxyhydroxide and losartan, furosemide, digoxin and warfarin. There is also a low risk of drug–drug interaction with omeprazole (based on AUC0–∞ values). Therefore, sucroferric oxyhydroxide may be administered concomitantly without the need to adjust the dosage regimens of these drugs.
Highlights
One of the serious and common clinical consequences of chronic kidney disease (CKD) is hyperphosphatemia, which is associated with CKD-mineral bone disorder [1], and increased risk of cardiovascular events [2] and mortality [3,4,5,6]
Systemic exposure based on AUC0–? for all drugs, and AUC0–24 for all drugs except omeprazole
There is a low risk of drug–drug interactions between sucroferric oxyhydroxide and losartan, furosemide, digoxin and warfarin
Summary
One of the serious and common clinical consequences of chronic kidney disease (CKD) is hyperphosphatemia, which is associated with CKD-mineral bone disorder [1], and increased risk of cardiovascular events [2] and mortality [3,4,5,6]. The novel polynuclear iron (III)-oxyhydroxide phosphate binder sucroferric oxyhydroxide is being investigated for the treatment of hyperphosphatemia. It is formulated as a chewable tablet that may be taken without water. A Phase II dose-finding study demonstrated that sucroferric oxyhydroxide doses of 1.0–2.5 g/day (based on iron content) significantly lowered serum. The novel iron-based phosphate binder sucroferric oxyhydroxide is being investigated for the treatment of hyperphosphatemia. Methods Five Phase I, single-center, open-label, randomized, three-period crossover studies in healthy volunteers investigated the effect of a single dose of sucroferric oxyhydroxide 1 g (based on iron content) on the pharmacokinetics of losartan 100 mg, furosemide 40 mg, omeprazole 40 mg, digoxin 0.5 mg and warfarin 10 mg. Pharmacokinetic parameters [including area under the plasma concentration– time curve (AUC) from time 0 extrapolated to infinite time (AUC0–?) and from 0 to 24 h (AUC0–24)] for these drugs were determined: alone in the presence of food; with sucroferric oxyhydroxide in the presence of food; 2 h after food and sucroferric oxyhydroxide administration
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