title: No effect of imidafenacin, a novel antimuscarinic drug, on digoxin pharmacokinetics in healthy subjects.
abstract: Plasma digoxin concentrations are increased by the coadministration of anticholinergic drugs, such as propantheline, which decrease gastrointestinal motility. The present study evaluated the effect of imidafenacin, a novel anticholinergic drug, on the pharmacokinetics of digoxin. The effect of imidafenacin on the pharmacokinetics of digoxin was examined in 14 healthy Japanese male subjects in a single-centre, open-label, randomized, two-way crossover study. Subjects received a daily oral dose of digoxin 0.25 mg on days 1 and 2 and digoxin 0.125 mg on days 3 to 8 (period 1). Following a 2-week washout period, digoxin was administered orally for 8 days in a similar manner (period 2). A twice daily dose of imidafenacin 0.1 mg was concomitantly administered with digoxin for 8 days either in period 1 or 2. The geometric mean ratios [GMR] (90% confidence intervals [CIs]) for digoxin C(max) and AUC(0-24) (with/without imidafenacin) at steady state were 0.88 (0.74, 1.04) and 1.00 (0.90, 1.10), respectively. The 90% CIs of GMR for digoxin trough concentration, urinary excretion amount and renal clearance at steady state fell within the range of 0.8 to 1.25. The steady-state pharmacokinetics of digoxin is not affected by concomitant administration of imidafenacin in healthy subjects.
authors.affiliation: Pharmacokinetic Research Laboratories, Ono Pharmaceutical Co., Ltd., Ibaraki, Japan. s.nakade@ono.co.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakade
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ohno
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakayama
authors.forename: Junsaku
authors.initials: J
authors.lastname: Kitagawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohnishi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyata
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*
chemical_list: D007093:Imidazoles; D018727:Muscarinic Antagonists; D004077:Digoxin; C120953:imidafenacin