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NCT Number: NCT00162474

Determinants of Warfarin Metabolism

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.

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Key information

Conditions

Healthy

Age range

20 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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)

Treatment and study plan

Warfarin

Drug

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

Phenytoin

Drug

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

Losartan & Hydrochlorothiazide

Drug

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

Flurbiprofen

Drug

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

Siponimod

Drug

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

Dicloxacillin

Drug

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.

Primary outcomes

  1. Warfarin oral clearance

    Time frame: 2 weeks

  2. Formation clearance of CYP2C9 mediated warfarin metabolites

    Time frame: 2 weeks

  3. Phenytoin Metabolic Ratio, oral clearance of Phenytoin, Formation clearance of p-HPPH.

    Time frame: Up to 4 days (96 hours) post drug intake.

    Following single dose administration of Phenytoin 300 mg, at least two blood samples 12 and 24 hours post drug intake will be obtained and urine will be collected for at least 24 hours.

  4. Losartan oral clearance and the formation clearance of E3174.

    Time frame: Up to 48 hours post drug intake.

    For those participant who receive losartan, blood sample will be collected periodically over 48 hours and urine will be collected for 48 hours. Losartan oral clearance and the formation clearance of E3174 will serve as primary outcomes.

  5. Flurbiprofen oral clearance.

    Time frame: Up to 36 hours post drug intake.

    Some participant will receive single dose of flurbiprofen 50 mg. Plasma samples will be obtained periodically over 24 hours and urine will be collected.

  6. Siponimod oral clearance.

    Time frame: Up to 2 weeks following drug intake.

    Some participants will receive single dose of siponimod 0.25 mg and blood samples will be obtained periodically over the next 2 weeks. Pharmacodynamic response will be evaluated by repeated ECG records and measurement of CBC and potassium.

  7. Change in S-warfarin and phenytoin pharmacokinetic parameters.

    Time frame: Up to 6 weeks following the administration of the first warfarin single dose.

    Some patients will receive phenytoin (300 mg) and at least one week later warfarin (20 mg) twice before and after intake of dicloxacillin 500 mg QID for 21 days.

  8. Correlation between CYP2C9 substrate pharmacokinetics and genetic polymorphism.

    Time frame: For up to 5 years following drug intake.

    Using candidate gene approach, sequencing of relevant regions in chromosome 10 will be conducted. Potential genetic alterations (SNPs, deletions, insertions, p-VNTR) will be correlated with pharmacokinetic parameters of CYP2C9 substrates.

Study contacts

Contact information is provided by the study sponsor or research team.

Yoseph Caraco, MD

CONTACT

[email protected]

00 972 2 6779373

Sponsors and collaborators

Lead sponsor

Hadassah Medical Organization

Other

Registry information

Official study title

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

Important dates

Study start
2003
Primary completion
2030
Study completion
2030
First posted
Sep 13, 2005
Registry last updated
Apr 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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