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dc.contributor.authorLesko, L.J.
dc.contributor.authorOffman, E.
dc.contributor.authorBrew, C.T.
dc.date.accessioned2019-07-15T16:12:06Z
dc.date.available2019-07-15T16:12:06Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85027411197&doi=10.1177%2f1074248417691135&partnerID=40&md5=279726306d369d39c8ea46d5c0ac4dfb
dc.identifier.urihttp://hdl.handle.net/10713/9886
dc.description.abstractIntroduction: 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. Copyright 2017 Author(s).en_US
dc.description.urihttps://www.doi.org/10.1177/1074248417691135en_US
dc.language.isoen_USen_US
dc.publisherSAGE Publications Ltden_US
dc.relation.ispartofJournal of Cardiovascular Pharmacology and Therapeutics
dc.subjectabsorptionen_US
dc.subjectdose separationen_US
dc.subjectdrug-drug interactionsen_US
dc.subjecthyperkalemiaen_US
dc.subjectpatiromeren_US
dc.subjectpotassium-binderen_US
dc.titleEvaluation of the Potential for Drug Interactions with Patiromer in Healthy Volunteersen_US
dc.typeArticleen_US
dc.identifier.doi10.1177/1074248417691135
dc.identifier.pmid28585859


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