Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers.
OBJECTIVE
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,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) 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.
Hua
Teng C
TC
Lilly NUS Centre for Clinical Pharmacology, National University of Singapore, Singapore.
Pan
Alan
A
Chan
Clark
C
Poo
Yeo K
YK
Skinner
Michael H
MH
Knadler
Mary P
MP
Gonzales
Celedon R
CR
Wise
Stephen D
SD
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000328:Adult; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000097:blood / Q000493:pharmacokinetics*; D003408:Cresols / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D010665:Phenylpropanolamine; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D000068737:Tolterodine Tartrate
D018759:Adrenergic Uptake Inhibitors; D001559:Benzhydryl Compounds; D003408:Cresols; D004338:Drug Combinations; D000068736:Duloxetine Hydrochloride; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; D000068737:Tolterodine Tartrate