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Evaluation of the Pharmacokinetic Interaction Between the β 3 ‐Adrenoceptor Agonist Mirabegron and the Muscarinic Receptor Antagonist Solifenacin In Healthy Subjects
Author(s) -
Krauwinkel Walter J. J.,
Kerbusch Virginie M. M.,
Meijer John,
Tretter Reiner,
Strabach Gregory,
Van Gelderen E. Marcel
Publication year - 2013
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.37
Subject(s) - solifenacin , mirabegron , medicine , overactive bladder , urology , muscarinic antagonist , pharmacology , agonist , antagonist , endocrinology , receptor , alternative medicine , pathology
Mirabegron, a selective β 3 ‐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.