Published in:
01-02-2001 | Original Research Article
Food Does Not Influence the Pharmacokinetics of a New Extended Release Formulation of Tolterodine for Once Daily Treatment of Patients with Overactive Bladder
Published in: Clinical Pharmacokinetics | Issue 2/2001
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Objective
To determine whether food intake influences the pharmacokinetics of a new, once daily, extended release (ER) capsule formulation of tolterodine in healthy volunteers, and to compare its bioavailability with that of the existing immediate release (IR) tablet.
Design
Open, randomised, 3-way crossover trial.
Participants
17 healthy volunteers (3 females, 14 males) aged between 19 and 50 years. With the exception of 1 male volunteer, all participants were classified as extensive metabolisers by cytochrome P450 2D6 genotyping.
Methods
Volunteers received single oral doses of tolterodine L-tartrate ER 8mg (2 × 4mg capsules) on an empty stomach or with a standardised high-fat breakfast. Reference therapy comprised tolterodine L-tartrate IR 4mg (2 × 2mg tablets), administered in the fasting state. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (sum of unbound tolterodine + 5-HM) were measured for up to 72 hours post-dose. Safety end-points were also determined.
Results
No effect of food on the bioavailability of tolterodine ER capsules was apparent and there was no sign of dose-dumping with meals. The geometric mean fed: fasting ratio of area under the serum concentration-time curve to infinity (AUC∞) of the active moiety, for all volunteers combined, was 0.95 (90% confidence interval 0.88 to 1.03). Equivalence with respect to AUC∞ (dose-corrected) was also found for the ER capsule compared with the IR tablet, although uncorrected maximum serum concentrations were around 50% lower despite the fact that the capsule dose was twice as high. Seven volunteers reported adverse events, predominantly headache. No volunteer reported dry mouth. Overall, there were no safety concerns.
Conclusions
The new ER formulation of tolterodine shows no pharmacokinetic interaction with food. On the basis of these results, patients with overactive bladder may, therefore, be advised to take the drug without regard to the timing of meals, maximising convenience during therapy.