Evaluation of the Pharmacokinetic Interaction Between the β3‐Adrenoceptor Agonist Mirabegron and the Muscarinic Receptor Antagonist Solifenacin In Healthy Subjects. Issue 3 (14th May 2013)

• Record Type: Journal Article
• Authors: Krauwinkel, Walter J. J.; Kerbusch, Virginie M. M.; Meijer, John; Tretter, Reiner; Strabach, Gregory; Van Gelderen, E. Marcel
• Is Part Of: Clinical pharmacology in drug development. Volume 2:Issue 3(2013:Jul.)
• Page Start: 255
• Page End: 263
• Publication Date: 2013-05-14
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.37
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd37-sec-0001" sec-type="section"> <p>Mirabegron, a selective β₃‐adrenoceptor agonist, is approved for the treatment of overactive bladder (OAB). Solifenacin is a muscarinic receptor antagonist widely used in the treatment of OAB. This open‐label, 1‐sequence, 2‐arm study investigated whether any pharmacokinetic interaction exists between mirabegron and solifenacin. In arm 1, 21 healthy men and women received 10 mg solifenacin succinate alone and in combination with mirabegron 100 mg qd. In arm 2, 20 healthy men and women received 100 mg mirabegron alone and in combination with solifenacin succinate 10 mg qd. Plasma samples were collected and tolerability was assessed. Following coadministration of mirabegron and solifenacin in arm 1, solifenacin geometric mean ratios (90% confidence interval [CI]) for C_max and AUC_inf were 1.23 (1.15, 1.31) and 1.26 (1.17, 1.35), respectively, compared with solifenacin alone, with a 1.07‐fold increase in mean t_1/2. In arm 2, mirabegron ratios (90% CI) for C_max and AUC_inf were 0.99 (0.78, 1.26) and 1.15 (1.01, 1.30), respectively, for the combination relative to mirabegron alone, with an increase in mean t_max of approximately 1 hour. Mirabegron or solifenacin alone or in combination was generally well tolerated.</p> </sec> </abstract>