Clinical pharmacology and therapeutics
-
Clin. Pharmacol. Ther. · Apr 2003
Randomized Controlled Trial Clinical TrialEffects of three fluoroquinolones on QT interval in healthy adults after single doses.
A clinical trial was conducted in healthy adult volunteers to assess the effect of levofloxacin, moxifloxacin, and ciprofloxacin on the QT and QTc interval. ⋯ A change in QTc (Bazett) interval from baseline can be demonstrated safely in healthy volunteers after single high doses of fluoroquinolones that achieve approximately 1.5 times the maximum plasma drug concentration that occurs after recommended doses. There is substantial daily variation in both QT and QTc interval, and the magnitude and frequency of changes in QTc interval can depend on the methods used. These factors need to be considered because clinical trials measuring the effects of drugs on QT intervals are used to estimate the risk of using these drugs. Greater changes in QT and QTc intervals after treatment with moxifloxacin compared with levofloxacin or ciprofloxacin are consistent with in vitro observations related to the effect of these drugs on rapid potassium (IK(r)) channels. The clinical relevance of these differences is not known.
-
Clin. Pharmacol. Ther. · Mar 2003
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers.
Duloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2). ⋯ Duloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine.