title: Investigation of multiple dose citalopram on the pharmacokinetics and pharmacodynamics of racemic warfarin.
abstract: OBJECTIVE
  An open, controlled, randomized, crossover study was conducted in healthy males to assess the possible occurrence of a pharmacokinetic/pharmacodynamic interaction between warfarin and the selective serotonin re-uptake inhibitor citalopram.
  
  
  METHODS
  Twelve subjects received a single 25 mg dose of racemic warfarin either alone or on Day 15 of a 21-day oral dosing regimen of 40 mg citalopram daily. Blood samples for pharmacokinetic analysis were obtained over a 168 h period after warfarin dosing. The degree of anticoagulation was assessed by the prothrombin time.
  
  
  RESULTS
  Citalopram produced no change in the pharmacokinetics of (R)- and (S)-warfarin, indicating that citalopram does not alter the metabolism of warfarin mediated via CYP1A2, CYP3A4 and CYP2C9. Citalopram coadministration resulted in a statistically significant increase in the maximum prothrombin time (R(max); by 1.6 +/- 3.0 s) and the area under the prothrombin time-time curve (AUC(PT); by 5.0 +/- 5.7%). The 90% confidence intervals for R(max) and AUC(PT) ratios (citalopram + warfarin/warfarin alone) were 1.01-1.10 and 1.03-1.07, respectively.
  
  
  CONCLUSIONS
  The small increase in prothrombin time observed in this study with coadministration of citalopram and warfarin is not considered to be of importance in the clinical setting.
authors.affiliation: H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Priskorn
authors.forename: J S
authors.initials: JS
authors.lastname: Sidhu
authors.forename: F
authors.initials: F
authors.lastname: Larsen
authors.forename: J D
authors.initials: JD
authors.lastname: Davis
authors.forename: A Z
authors.initials: AZ
authors.lastname: Khan
authors.forename: P E
authors.initials: PE
authors.lastname: Rolan
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008297:Male; D012016:Reference Values; D013237:Stereoisomerism; D014859:Warfarin / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D015283:Citalopram; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System