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Determinants of Warfarin Metabolism

ConditionHealthy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age20-50
SponsorHadassah Medical Organization

About this trial

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 criteria

This trial accepts healthy volunteers

Qualifiers

Age range of 20-50 years old

The absence of significant disease states

Disqualifiers

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)

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

Treatment groups

1,000 Participants
are divided into 1 treatment group
Group A: CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.Experimental treatment 6 interventions

Trial outcomes

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.

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.

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

Losartan oral clearance and the formation clearance of E3174.

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.

Time frame
Up to 48 hours post drug intake.

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Hadassah Medical Organization

Lead sponsor

Source ClinicalTrials.gov
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