Short-term clarithromycin administration impairs clearance and enhances pharmacodynamic effects of trazodone but not of zolpidem.
The kinetic and dynamic interactions of 5 mg zolpidem and 50 mg trazodone with 500 mg clarithromycin (4 doses given over 32 h) were investigated in a 5-way double crossover study with 10 healthy volunteers. The five treatment conditions were: placebo + placebo; zolpidem + placebo; zolpidem + clarithromycin; trazodone + placebo; and trazodone + clarithromycin. Coadministration of clarithromycin increased trazodone area under the curve, prolonged elimination half-life, increased peak plasma concentration (C(max)), and reduced oral clearance. In contrast, clarithromycin had no significant effect on any kinetic parameter for zolpidem. Clarithromycin did not potentiate sedation caused by zolpidem. However, clarithromycin coadministered with trazodone significantly increased self- and observer-rated sedation and ratings of feeling "spacey." Thus, short-term clarithromycin coadministration significantly impairs trazodone clearance, elevates plasma concentrations, and enhances sedative effects. However, clarithromycin has no significant kinetic or dynamic interaction with zolpidem.
Farkas
D
D
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts, USA.
Volak
L P
LP
Harmatz
J S
JS
von Moltke
L L
LL
Court
M H
MH
Greenblatt
D J
DJ
D000328:Adult; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D017291:Clarithromycin / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology; D014196:Trazodone / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077334:Zolpidem
D014151:Anti-Anxiety Agents; D000900:Anti-Bacterial Agents; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem; D017291:Clarithromycin; D014196:Trazodone