Prediction of Drug Interactions With CYP2C9 Substrates

Sponsor

Hadassah Medical Organization (Other)

Overall Status

Completed

CT.gov ID

NCT00226538

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

CYP2C9, is one of the major drug metabolism enzymes accounting for about 20% of the hepatic cytochrome P450 content and being second only to CYP3A4.

The proposed study will explore different possible drug interactions with CYP2C9 substrates by evaluating the effect of prototype inducers and inhibitors on the phenotypic trait measurement. It is expected that the identification of drugs that might interact with CYP2C9 substrates will be used to rationalize future drug interaction studies designed to evaluate the actual magnitude of effect and its clinical implications. This approach should be particularly useful when applied to those CYP2C9 drugs characterized by a narrow therapeutic index (i.e. warfarin).

This study will consist of three study periods separated from each other by a two weeks washout period. In the course of the study the subjects will receive in a double blind, crossover fashion, rifampin 300 mg. twice daily, diclofenac 50 mg twice daily. and fluconazole 200 mg. twice daily, each for one week. All drugs will be administered as identical looking tablets that will be prepared at the pharmacy of the Hadassah University Hospital and their order of administration will be randomized.On the day prior to, on day 6 of and 7 days following each drug period, the activity of CYP2C9 will be evaluated by the administration of a single phenytoin 300 mg. dose. The subjects will be requested to collect their urine for 24 hours and a single blood sample will be obtained 12 hours post phenytoin intake.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Phenytoin Drug: Rifampicin Drug: Diclophenac Drug: Fluconazole	N/A

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double

Official Title:

Prediction of Potential Drug Interaction With CYP2C9 Substrate by Using Phenytoin Metabolic Ratio as a Marker of Its Activity in-Vivo.

Study Start Date :

Aug 1, 1999

Outcome Measures

Primary Outcome Measures

Phenytoin metabolic ratio prior to and following exposure to fluconazole, diclophenac and rifampicin. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age range 20-50
Absence of significant disease states

Exclusion Criteria:

Known hypersensitivity to one of the drugs used in the study
Significant disease states
Regular use of drugs (including birth control pills)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hadassah Medical Organization	Jerusalem		Israel

Sponsors and Collaborators

Hadassah Medical Organization

Investigators

Principal Investigator: Yoseph Caraco, MD, Hadassah Medical Organization

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00226538

Other Study ID Numbers:

yc19555-HMO-CTIL

First Posted:

Sep 27, 2005

Last Update Posted:

Oct 29, 2008

Last Verified:

Oct 1, 2008

Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 29, 2008