Pharmacogenetics of Warfarin Induction and Inhibition

Summary

This research study will help determine how a person's genetic makeup affects their response to drugs, the ability of the body to break down drugs, and their potential to experience an interaction between drugs. The investigators are investigating the drug interactions with the commonly used anticoagulant drug called warfarin. Warfarin is used for the treatment and prevention of life-threatening abnormal blood clots such as deep vein thrombosis, heart attacks, and strokes. The investigators chose warfarin for this study because it is a commonly used drug and must be monitored closely to avoid side effects. The investigators are interested in studying whether individuals with certain genetic profiles react differently to warfarin when it is combined with other drugs. This research is being done to see if certain genetic profiles require us to adjust warfarin doses differently than is needed for the general population. Genetic profiles of subjects are determined from their participation in the Pharmacogenetics Registry study (investigator Richard Brundage, University of Minnesota).

The study hypothesis is: Functionally defective CYP2C9 alleles attenuate the warfarin-fluconazole inhibitory interaction and exacerbate the warfarin-rifampin inductive interaction.

Conditions

• Healthy

Interventions

DRUG

Control - Warfarin only

A single 10 mg warfarin dose taken at the start of the study period. No other medications taken during this study period.

DRUG

Fluconazole - Warfarin

A single 10 mg warfarin dose taken at the start of the study period. 400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.

DRUG

Rifampin - Warfarin

A single 10 mg warfarin dose taken at the start of the study period. 300 mg rifampin taken every morning starting a week before the start of the study period and continuing throughout the study period.

Sponsors & Collaborators

• National Institute of General Medical Sciences (NIGMS)

  collaborator NIH

• University of Minnesota

  lead OTHER

Principal Investigators

• Richard Brundage, PhD · University of Minnesota

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-05-31

Primary Completion

2013-06-30

Completion

2013-06-30

Countries

• United States

Study Locations