Evaluation of the Pharmacokinetic Interaction Between the β3 -Adrenoceptor Agonist Mirabegron and the Muscarinic Receptor Antagonist Solifenacin In Healthy Subjects.
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 Cmax and AUCinf 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 t1/2 . In arm 2, mirabegron ratios (90% CI) for Cmax and AUCinf 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 tmax of approximately 1 hour. Mirabegron or solifenacin alone or in combination was generally well tolerated.
Astellas Pharma Europe BV, Leiderdorp, The Netherlands.
Walter J J
WJ
Krauwinkel
PharmAspire Consulting, Wijchen, The Netherlands.
Virginie M M
VM
Kerbusch
Astellas Pharma Europe BV, Leiderdorp, The Netherlands.
John
J
Meijer
Astellas Pharma Europe BV, Leiderdorp, The Netherlands.
Reiner
R
Tretter
Société Générale de Surveillance (SGS), Paris, France.
Gregory
G
Strabach
Astellas Pharma Europe BV, Leiderdorp, The Netherlands.
E Marcel
EM
Van Gelderen
interaction; mirabegron; pharmacokinetic; solifenacin; β3-adrenoceptor