Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers.

Aim To investigate the effect of duloxetine on the pharmacokinetics and tolerability of tolterodine and its active 5-hydroxymethyl metabolite (5-HM). Methods Sixteen healthy subjects received two 5-day treatment regimens in a randomized, double-blinded, crossover fashion: tolterodine (2 mg, BID) +duloxetine (40 mg, BID), tolterodine (2 mg, BID) +duloxetine placebo (BID). Plasma concentrations of tolterodine and 5-HM were measured on day 5. Adverse events, clinical safety laboratory data and vital signs were assessed during the study. Results Duloxetine increased the AUC(tau,ss) of tolterodine by 71% [geometric mean, 95% confidence interval (CI) 31, 123], and its C-max,C-ss by 64% (CI 30, 106), and prolonged its t(1/2) by 14% (CI 1, 28). Duloxetine did not affect the plasma concentrations or t(1/2) 2 of 5-HM. Laboratory data and vital signs did not reveal any clinically significant changes or abnormalities. Conclusions Duloxetine exhibited minor inhibitory effects on the pharmacokinetics of tolterodine but not 5-HM. Coadministration of these drugs was well tolerated and demonstrated no significant safety findings in the studied population. These findings suggest that there should not be a need for routine adjustment of tolterodine dosage in the presence of duloxetine.