Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers

Article date: May 2004

By: Teng C. Hua, Alan Pan, Clark Chan, Yeo K. Poo, Michael H. Skinner, Mary P. Knadler, Celedon R. Gonzales, Stephen D. Wise, in Volume 57, Issue 5, pages 652-656


To investigate the effect of duloxetine on the pharmacokinetics and tolerability of tolterodine and its active 5‐hydroxymethyl metabolite (5‐HM).


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.


Duloxetine increased the AUCτ,ss of tolterodine by 71%[geometric mean, 95% confidence interval (CI) 31, 123], and its Cmax,ss by 64% (CI 30, 106), and prolonged its t1/2 by 14% (CI 1, 28). Duloxetine did not affect the plasma concentrations or t1/2 of 5‐HM. Laboratory data and vital signs did not reveal any clinically significant changes or abnormalities.


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.

DOI: 10.1111/j.1365-2125.2004.02068.x

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