title: The effect of fluvoxamine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects.
abstract: 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.
authors.affiliation: Clinical Pharmacology, Astellas Pharma Inc., 3-17-1 Hasune, Itabashi-ku, Tokyo 174-8612, Japan. takeshi.kadokura@jp.astellas.com
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kadokura
authors.forename: Martin
authors.initials: M
authors.lastname: den Adel
authors.forename: Walter J J
authors.initials: WJ
authors.lastname: Krauwinkel
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takeshige
authors.forename: Akito
authors.initials: A
authors.lastname: Nishida
mesh_terms: 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*
chemical_list: D001562:Benzimidazoles; D016666:Fluvoxamine; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C071315:ramosetron