Prediction of Drug Interactions With CYP2C9 Substrates

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00226538
• Other study ID #: yc19555-HMO-CTIL
• Status: Completed
• Phase: N/A
• First received: September 12, 2005
• Last updated: October 28, 2008
• Start date: August 1999

Study information

• Verified date: October 2008
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 50 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double-Blind

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Phenytoin

• Rifampicin

• Diclophenac

• Fluconazole

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenytoin metabolic ratio prior to and following exposure to fluconazole, diclophenac and rifampicin.