Effects of Genotype on CYP2C9 Drug Interactions

Summary

This research study will help determine how a person's genetic makeup affects their responses to drugs, the ability of the body to break down drugs, and their potential to experience an interaction between drugs. We are investigating the drug interactions between an antifungal drug called fluconazole and the commonly used drugs tolbutamide, flurbiprofen, and ketoprofen. Tolbutamide is used for management of Type 2 diabetes. Both flurbiprofen and ketoprofen are non-steroidal anti-inflammatory drugs (NSAIDs) often used for arthritis or pain. We are interested in studying whether individuals with certain genetic profiles have different drug interactions than normal. This research is being done to see if certain genetic profiles require us to adjust medication doses differently than is needed for the general population. Genetic profiles of subjects are determined from their previous participation in the Pharmacogenetics Registry (Investigator Richard Brundage, University of Minnesota).

The study hypothesis is: Fraction metabolized by CYP2C9 enzyme determines the extent of drug interactions in CYP2C9\*1/\*1 individuals but this factor (fraction metabolized) becomes less influential and drug interactions are attenuated in a gene-dose dependent manner in individuals with one or more defective alleles.

Conditions

• Healthy

Interventions

DRUG

Flurbiprofen Control - Flurbiprofen Only

A single 50 mg flurbiprofen dose taken at the start of the study period. No other drugs administered during this study period.

DRUG

Flurbiprofen Inhibition - Flurbiprofen & Fluconazole

A single 50 mg flurbiprofen 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

Ketoprofen Control - Ketoprofen Only

A single 75 mg ketoprofen dose taken at the start of the study period. No other drugs administered during this study period.

DRUG

Ketoprofen Inhibition - Ketoprofen & Fluconazole

A single 75 mg ketoprofen 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

Tolbutamide Control - Tolbutamide Only

A single 500 mg tolbutamide dose taken at the start of the study period. No other drugs administered during this study period.

DRUG

Tolbutamide Inhibition - Tolbutamide & Fluconazole

A single 500 mg tolbutamide 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.

Sponsors & Collaborators

• National Institute of General Medical Sciences (NIGMS)

  collaborator NIH

• University of Minnesota

  lead OTHER

Principal Investigators

• Richard Brundage, PhD · University of Minnesota

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-12-31

Primary Completion

2014-06-30

Completion

2014-06-30

Countries

• United States

Study Locations