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Combined administration of duloxetine (DU) and lorazepam (LO): A pharmacokinetic (PK) and pharmacodynamic (PD) study
Author(s) -
Chalon S.,
Vandenhende F.,
Ertle S.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.141
Subject(s) - digit symbol substitution test , crossover study , placebo , pharmacodynamics , duloxetine , medicine , pharmacology , pharmacokinetics , anesthesia , psychology , alternative medicine , pathology
Background/Aims DU is a relatively balanced and potent dual inhibitor of norepinephrine and serotonin transporters, indicated for depression and targeted for female stress urinary incontinence. To assess possible DU‐LO interaction, a randomized, double‐blind, two‐period, crossover study was conducted in 16 healthy subjects. Methods DU (60mg BID) or placebo was given for 8 days; LO (2 mg BID) was given from Day 5 to Day 8. PK profiles (DU and LO) were obtained on Day 4 (DU alone) and Day 8 (DU+ LO or LO alone). Critical Flicker Fusion Threshold (CFFT), Multiple Choice Reaction Time (MCRT), Digit Symbol Substitution Test (DSST) and the Bond and Lader Scale (BL) were administered at regular intervals on Days 4, 5 and 8. Immediate and Delayed Word Recall tests were performed on Days 4 and 8. Results No significant PK interaction was detected. On Day 4, DU alone produced small but statistically significant impairments of vigilance on DSST, MCRT and subjective alertness (BL) but no effect on other parameters. Compared to LO alone, LO+DU (Day 5) led to a decreased vigilance on DSST, MCRT and BL without altering the amnestic effects of LO. The difference between the two combinations overall tended to remit from Day 5 (first LO dose) to Day 8. Conclusions These data suggest that caution should be exercised when LO and DU are co‐administered due to the potential for an increase in LO‐induced sedation. Clinical Pharmacology & Therapeutics (2005) 77 , P65–P65; doi: 10.1016/j.clpt.2004.12.141