title: Effect of pitavastatin vs. rosuvastatin on international normalized ratio in healthy volunteers on steady-state warfarin.
abstract: OBJECTIVE
  Statins have been shown to impact international normalized ratio (INR) when coadministered with warfarin. The aim of this study was to assess the effect of pitavastatin compared with rosuvastatin on steady-state pharmacodynamics (PD) of warfarin by measuring INR in healthy adult subjects.
  
  
  METHODS
  Subjects received oral doses of warfarin 5 mg once daily on days 1 through 3. The dose was titrated on days 4 through 9 to reach a steady-state INR of 1.5 to 2.2. Warfarin was continued on days 10 through 21 and pitavastatin 4 mg or rosuvastatin 40 mg was administered once daily on days 14 through 22. After a 14-day washout period, the process was repeated with the alternate statin. STUDY NUMBER: NK-104-4.03US.
  
  
  RESULTS
  For pitavastatin, mean INR changed from 1.73 ± 0.18 (n = 42) on day 14 before starting statin dosing, to 1.78 ± 0.29 (n = 42) on day 22 at treatment end; the difference in INR was not significant (p = 0.219). For rosuvastatin, mean INR increased significantly from 1.74 ± 0.20 (n = 43) at baseline to 1.90 ± 0.30 (n = 43) at treatment end (p < 0.001). Rosuvastatin caused a significantly greater increase in INR than pitavastatin (p < 0.001).
  
  
  CONCLUSIONS
  Steady-state INR during warfarin treatment did not change significantly when pitavastatin 4 mg was added to the regimen, while a significant increase was observed when rosuvastatin 40 mg was added. The effect of rosuvastatin on INR was significantly larger than the effect of pitavastatin. This study is limited because it was done in healthy volunteers. Further studies in patient populations are needed to better understand the clinical significance of the results.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA. yucy@lilly.com
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Yu
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Campbell
authors.forename: Baojin
authors.initials: B
authors.lastname: Zhu
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Knadler
authors.forename: David S
authors.initials: DS
authors.lastname: Small
authors.forename: Craig A
authors.initials: CA
authors.lastname: Sponseller
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hunt
authors.forename: Roger E
authors.initials: RE
authors.lastname: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; D013449:Sulfonamides; D014859:Warfarin; D000068718:Rosuvastatin Calcium; C108475:pitavastatin