The effect of fluvoxamine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects.
OBJECTIVE
To investigate the effects of multiple doses of fluvoxamine on the pharmacokinetics, safety, and tolerability of a single oral 10-mug dose of ramosetron.


METHODS
This was a single-center, open, one-sequence cross-over study. On Day 1, healthy male and female subjects were administered a single dose of 10 mug ramosetron. Dosing of fluvoxamine started with an initial morning dose of 50 mg on Day 3, followed by a twice daily (12-h interval) dosing of 50 mg on Days 4-12. The morning dose on Day 11 was administered in combination with a single dose of 10 mug ramosetron.


RESULTS
Co-administration of fluvoxamine with ramosetron resulted in an increase in the C(max) and AUC(0-inf) of ramosetron by 1.42-fold (90% CI 1.35-1.49) and 2.78-fold (90% CI 2.53-3.05), respectively.


CONCLUSIONS
Co-administration of the CYP1A2 inhibitor fluvoxamine with ramosetron resulted in an interaction. However, the safety data collected during the study do not indicate that this interaction will cause any major safety concerns.
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; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D001562:Benzimidazoles; D016666:Fluvoxamine; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C071315:ramosetron