RecruitingNot ApplicableNCT00162474

Determinants of Warfarin Metabolism

Correlation Between Phenotypic Activity of CYP2C9 and Genetic Polymorphism in CYP2C9 and Warfarin Metabolism.


Sponsor

Hadassah Medical Organization

Enrollment

1,000 participants

Start Date

Sep 1, 2003

Study Type

INTERVENTIONAL

Conditions

Summary

The anticoagulant effect of warfarin varies greatly among individuals. Some of this variability is attributed to differences in the activity of CYP2C9, the predominant enzyme involved in the metabolism of S-warfarin. The present study is designed to define the differences in warfarin metabolism among healthy individuals carrying different CYP2C9 genotypes. In addition, the study will define the correlation between the phenytoin metabolic ratio, a marker of CYP2C9 activity in vivo, and warfarin metabolism.


Eligibility

Min Age: 20 YearsMax Age: 50 Years

Inclusion Criteria2

  • Age range of 20-50 years old
  • The absence of significant disease states

Exclusion Criteria4

  • Known hypersensitivity to warfarin or phenytoin
  • Known hepersensitivity to penicillins or cephalosporins (Dicloxacillin part)
  • The presence of significant disease states
  • Regular use of drugs (including birth control pills)

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Interventions

DRUGWarfarin

Each participant may be given at least one CYP2C9 substrate from the following list: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.

DRUGPhenytoin

Each participant may be given at least one CYP2C9 substrate from the following list: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.

DRUGLosartan & Hydrochlorothiazide

Each participant may be given at least one CYP2C9 substrate from the following list: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.

DRUGFlurbiprofen

Each participant may be given at least one CYP2C9 substrate from the following list: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.

DRUGSiponimod

Each participant may be given at least one CYP2C9 substrate from the following list: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.

DRUGDicloxacillin

To explore possible effect of dicloxacillin on CYP2C9 activity, some participants will be administered single dose of warfarin and phenytoin before and after intake of dicloxacillin.


Locations(1)

Hadassah Medical Organization

Jerusalem, Israel

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NCT00162474


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