Assessment of the effects of renal impairment on the pharmacokinetic profile of fesoterodine.
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.
Malhotra
Bimal
B
Pfizer Inc, 685 3rd Avenue, New York, NY 10017, USA. bimal.k.malhotra@pfizer.com
Gandelman
Kuan
K
Sachse
Richard
R
Wood
Nolan
N
D000284:Administration, Oral; D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects* / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*; D013997:Time Factors
D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; C526675:fesoterodine; D003404:Creatinine