Evaluation of the Potential for Drug Interactions with Patiromer in Healthy Volunteers
Date
2017Journal
Journal of Cardiovascular Pharmacology and TherapeuticsPublisher
SAGE Publications LtdType
Article
Metadata
Show full item recordAbstract
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. Copyright 2017 Author(s).Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85027411197&doi=10.1177%2f1074248417691135&partnerID=40&md5=279726306d369d39c8ea46d5c0ac4dfb; http://hdl.handle.net/10713/9886ae974a485f413a2113503eed53cd6c53
10.1177/1074248417691135
Scopus Count
Collections
Related articles
- Investigation of bioequivalence of a new fixed-dose combination of acarbose and metformin with the corresponding loose combination as well as the drug-drug interaction potential between both drugs in healthy adult male subjects.
- Authors: Kim S, Jang IJ, Shin D, Shin DS, Yoon S, Lim KS, Yu KS, Li J, Zhang H, Liu Y, Brendel E, Blode H, Wang Y
- Issue date: 2014 Aug
- Differential pharmacokinetics of diclofenac potassium for oral solution vs immediate-release tablets from a randomized trial: effect of fed and fasting conditions.
- Authors: Chen C, Bujanover S, Kareht S, Rapoport AM
- Issue date: 2015 Feb
- Pharmacokinetics of the New Hepatitis C Virus NS3 Protease Inhibitor Narlaprevir following Single-Dose Use with or without Ritonavir in Patients with Liver Cirrhosis.
- Authors: Isakov V, Koloda D, Tikhonova N, Kikalishvili T, Krasavina E, Lekishvili K, Malaya I, Ryska M, Samsonov M, Tolkacheva V
- Issue date: 2016 Dec
- Effect of coadministration of metformin with mirogabalin: Results from a phase 1, randomized, open-label, drug-drug interaction study .
- Authors: Dow J, Currie A, He L, Zaidi F, Zahir H
- Issue date: 2018 Oct
- Evaluation of the effects of formulation and food on the pharmacokinetics of lenvatinib (E7080) in healthy volunteers.
- Authors: Shumaker R, Aluri J, Fan J, Martinez G, Ren M, Chen K
- Issue date: 2014 Apr