Premium
Assessment of the Effects of Renal Impairment on the Pharmacokinetic Profile of Fesoterodine
Author(s) -
Malhotra Bimal,
Gandelman Kuan,
Sachse Richard,
Wood Nolan
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009332434
Subject(s) - pharmacokinetics , medicine , renal function , urology , creatinine , area under the curve , renal physiology , pharmacology , endocrinology
The effects of renal impairment on the pharmacokinetics of a single 4‐mg oral dose of fesoterodine are assessed in 8 healthy subjects and 8 subjects each with mild, moderate, or severe renal impairment. Compared with findings in healthy subjects, the maximum concentration in plasma of 5‐hydroxymethyl tolterodine (5‐HMT), the principal active moiety of fesoterodine, increases by 1.4‐, 1.5‐, and 2.0‐fold and area under the curve increases by 1.6‐, 1.8‐, and 2.3‐fold in subjects with mild, moderate, and severe renal impairment, respectively. There is a clear correlation between the renal clearance of 5‐HMT and creatinine clearance. The median time of observed maximum drug concentration (5–6 hours) and mean terminal half‐life (6–7 hours) of 5‐HMT are unaffected by renal impairment. The unbound fraction of 5‐HMT in plasma (0.43–0.54 ng/mL) is comparable across all groups. In conclusion, because of the involvement of both metabolic and renal elimination pathways, only modest increases in 5‐HMT exposures are observed in patients with renal impairment.