Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects.
BACKGROUND
The 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.


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.


RESULTS
Systemic 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.


CONCLUSIONS
There 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.
Vifor Pharma, Clinical Development, Aspreva International Ltd., 1203, 4464 Markham Street, Victoria, BC, V8Z 7X8, Canada. edward.chong@viforpharma.com.
Edward
E
Chong
Vifor Pharma, Clinical Development, Aspreva International Ltd., 1203, 4464 Markham Street, Victoria, BC, V8Z 7X8, Canada.
Veena
V
Kalia
PRA International, Lenexa, KS, USA.
Sandra
S
Willsie
Anaheim Clinical Trials, Anaheim, CA, USA.
Peter
P
Winkle
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018570:Risk Assessment; D013395:Sucrose / Q000008:administration & dosage* / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D000925:Anticoagulants; D002316:Cardiotonic Agents; D002614:Chelating Agents; D004232:Diuretics; D004338:Drug Combinations; D005290:Ferric Compounds; D054328:Proton Pump Inhibitors; C000599459:sucroferric oxyhydroxide; D013395:Sucrose; D014859:Warfarin; D004077:Digoxin; D005665:Furosemide; D019808:Losartan; D009853:Omeprazole
Chronic kidney disease; Hyperphosphatemia; Pharmacokinetics; Phase I; Sucroferric oxyhydroxide