Detrol LA - Clinical Pharmacology

(Page 4)

The elimination half-life of tolterodine immediate release for both males and females is 2.4 hours, and the half-life of the 5-hydroxymethyl metabolite is 3.0 hours in females and 3.3 hours in males.

Race:

Pharmacokinetic differences due to race have not been established.

Renal Insufficiency:

Renal impairment can significantly alter the disposition of tolterodine immediate release and its metabolites. In a study conducted in patients with creatinine clearance between 10 and 30 mL/ min, tolterodine imme-diate release and the 5-hydroxymethyl metabolite levels were approximately 2-3 fold higher in patients with renal impairment than in healthy volunteers. Exposure levels of other metabolites of tolterodine (eg, tolterodine acid, N-dealkylated tolterodine acid, N-dealkylated tolterodine and N-dealkylated hydroxy tolterodine) were significantly higher (10-30 fold) in renally impaired patients as compared to the healthy volunteers. The recommended dose for patients with significantly reduced renal function is tolterodine 2 mg daily (see PRECAUTIONS, General).

Hepatic Insufficiency:

Liver impairment can significantly alter the disposition of tolterodine immediate release. In a study of tolterodine immediate release conducted in cirrhotic patients, the elimination half-life of tolterodine immediate release was longer in cirrhotic patients (mean, 7.8 hours) than in healthy, young, and elderly volunteers (mean, 2 to 4 hours). The clearance of orally administered tolterodine immediate release was substantially lower in cirrhotic patients (1.0 ± 1.7 L/ h/ kg) than in the healthy volunteers (5.7 ± 3.8 L/ h/ kg). The recommended dose for patients with significantly reduced hepatic function is tolterodine 2 mg daily (see PRECAUTIONS, General).

CLINICAL STUDIES

DETROL LA Capsules 2 mg were evaluated in 29 patients in a Phase 2 dose-effect study. DETROL LA 4 mg was evaluated for the treatment of overactive bladder with symptoms of urge urinary incontinence and frequency in a ran-domized, placebo-controlled, multicenter, double-blind, Phase 3, 12-week study. A total of 507 patients received DETROL LA 4 mg once daily in the morning and 508 received placebo. The majority of patients were Caucasian (95%) and female (81%), with a mean age of 61 years (range, 20 to 93 years). In the study, 642 patients (42%) were 65 to 93 years of age.