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J Cardiovasc Pharmacol Ther. 2017 Sep;22(5):434-446. doi: 10.1177/1074248417691135. Epub 2017 Feb 13.

Evaluation of the Potential for Drug Interactions With Patiromer in Healthy Volunteers.

Author information

1
1 Center for Pharmacometrics and Systems Pharmacology, University of Florida College of Pharmacy, Orlando, FL, USA.
2
2 Clinical Pharmacology and Pharmacometrics, Celerion, Montreal, Quebec, Canada.
3
3 Research Biology, Relypsa, Inc, Redwood City, CA, USA.
4
4 Clinical Development, Relypsa, Inc, Redwood City, CA, USA.
5
5 Consultant, Relypsa, Inc, Redwood City, CA, USA.
6
6 Medical and Scientific Affairs, Relypsa, Inc, Redwood City, CA, USA.
7
7 Biometrics, Relypsa, Inc, Redwood City, CA, USA.
8
8 Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

INTRODUCTION:

Patiromer is a potassium-binding polymer that is not systemically absorbed; however, it may bind coadministered oral drugs in the gastrointestinal tract, potentially reducing their absorption.

METHODS:

Twelve randomized, open-label, 3-period, 3-sequence crossover studies were conducted in healthy volunteers to evaluate the effect of patiromer (perpetrator drug) on absorption and single-dose pharmacokinetics (PK) of drugs (victims) that might be commonly used with patiromer. Subjects received victim drug alone, victim drug administered together with patiromer 25.2 g (highest approved dose), and victim drug administered 3 hours before patiromer 25.2 g. The primary PK endpoints were area under the curve (AUC), extrapolated to infinity (AUC0-∞), and maximum concentration ( Cmax). Results were reported as 90% confidence intervals (CIs) about the geometric mean AUC0-∞ and Cmax ratios with prespecified equivalence limits of 80% to 125%.

RESULTS:

Overall, 370 subjects were enrolled, with 365 receiving ≥1 dose of patiromer; 351 subjects completed the studies and all required treatments. When coadministered with patiromer, the 90% CIs for AUC0-∞ remained within 80% to 125% for 9 drugs (amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil, and warfarin). The AUC0-∞ point estimate ratios for levothyroxine and metformin with patiromer coadministration were ≥80%, with the lower bounds of the 90% CIs at 76.8% and 72.8%, respectively. For ciprofloxacin, the point estimate for AUC0-∞ was 71.5% (90% CI: 65.3-78.4). For 8 of 12 drugs, point estimates for Cmax were ≥80% with patiromer coadministration; for ciprofloxacin, clopidogrel, metformin, and metoprolol, the point estimates were <80%. When patiromer was administered 3 hours after each victim drug, the 90% CIs for AUC0-∞ and Cmax for each drug were within the prespecified 80% to 125% limits.

CONCLUSION:

For 9 of the 12 drugs coadministered with patiromer, there were no clinically significant drug-drug interactions. For 3 drugs (ciprofloxacin, levothyroxine, and metformin), a 3-hour separation between patiromer and their administration resulted in no clinically significant drug-drug interactions.

KEYWORDS:

absorption; dose separation; drugdrug interactions; hyperkalemia; patiromer; potassium-binder

PMID:
28585859
PMCID:
PMC5555446
DOI:
10.1177/1074248417691135
[Indexed for MEDLINE]
Free PMC Article

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