Determinants of Warfarin Metabolism

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.

Conditions

• Healthy

Interventions

DRUG

Warfarin

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

DRUG

Phenytoin

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

DRUG

Losartan & Hydrochlorothiazide

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

DRUG

Flurbiprofen

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

DRUG

Siponimod

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

DRUG

Dicloxacillin

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.

Sponsors & Collaborators

• Hadassah Medical Organization

  lead OTHER

Principal Investigators

• Yoseph Caraco, MD · Hadassah Medical Organization

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

20 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2003-09-30

Primary Completion

2030-12-31

Completion

2030-12-31

Countries

• Israel

Study Locations