Detrol LA - Clinical Pharmacology

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A summary of mean (± standard deviation) pharmacokinetic parameters of tolterodine extended release and the 5-hydroxymethyl metabolite in extensive (EM) and poor (PM) metabolizers is provided in Table 1. These data were obtained following single and multiple doses of tolterodine extended release administered daily to 17 healthy male volunteers (13 EM, 4 PM).

Pharmacokinetics in Special Populations

Age:

In Phase 1, multiple-dose studies in which tolterodine immediate release 4 mg (2 mg bid) was administered, serum concentrations of tolterodine and of the 5-hydroxymethyl metabolite were similar in healthy elderly volunteers (aged 64 through 80 years) and healthy young volunteers (aged less than 40 years). In another Phase 1 study, elderly volunteers (aged 71 through 81 years) were given tolterodine immediate release 2 or 4 mg (1 or 2 mg bid). Mean serum concen-trations of tolterodine and the 5-hydroxymethyl metabolite in these elderly volunteers were approximately 20% and 50% higher, respectively, than reported in young healthy volunteers. However, no overall differences were observed in safety between older and younger patients on tolterodine in the Phase 3, 12-week, controlled clinical studies; therefore, no tolterodine dosage adjustment for elderly patients is recommended (see PRECAUTIONS, Geriatric Use).

Pediatric: The pharmacokinetics of tolterodine has not been established in pediatric patients.

Gender

The pharmacokinetics of tolterodine immediate release and the 5-hydroxymethyl metabolite are not influenced by gender. Mean Cmax of tolterodine immediate release (1.6 µg/ L in males versus 2.2 µg/ L in females) and the active 5-hydroxymethyl metabolite (2.2 µg/ L in males versus 2.5 µg/ L in females) are similar in males and females who were administered tolterodine immediate release 2 mg. Mean AUC values of tolterodine (6.7 µg° h/ L in males versus 7.8 µg° h/ L in females) and the 5-hydroxymethyl metabolite (10 µg° h/ L in males versus 11 µg° h/ L in females) are also similar.