The effect of paroxetine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects.
OBJECTIVE
The aim of our study was to investigate the effects of multiple doses of paroxetine on the pharmacokinetics, safety, and tolerability of a single oral 10-microg dose of ramosetron. METHODS This was an open, one-sequence crossover design study. On day 1, healthy male and female subjects were administered a single dose of 10 microg ramosetron. On the morning of day 3, the subjects were administered paroxetine to reach steady state, which consisted of morning doses of 20 mg on days 3-12. The dose on day 11 was administered in combination with a single dose of 10 microg ramosetron.


RESULTS
In subjects genotyped as extensive CYP2D6 metabolizers, coadministration of paroxetine with ramosetron resulted in an increase in area under the curve from 0 to infinity (AUC(0-inf)) and the peak concentration (Cmax) of ramosetron by 1.14-fold (90% confidence interval (CI): 1.07-1.22) and by 1.06-fold (90% CI: 1.00-1.11), respectively.


CONCLUSIONS
It can be concluded that the single-dose pharmacokinetic profile of ramosetron 10 microg is not affected to a clinically relevant degree by paroxetine 20 mg once daily administered for 10 days.
Kadokura
Takeshi
T
Clinical Pharmacology, Astellas Pharma Inc., 3-17-1, Hasune, Itabashi-ku, Tokyo 174-8612, Japan. takeshi.kadokura@jp.astellas.com
den Adel
Martin
M
Krauwinkel
Walter J J
WJ
Takeshige
Tetsuo
T
Nishida
Akito
A
D000328:Adult; D001562:Benzimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D001562:Benzimidazoles; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D017374:Paroxetine; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C071315:ramosetron; C504573:CYP1A2 protein, human