Prediction of Drug Interactions With CYP2C9 Substrates

NCT00226538 | Completed

• 1 other identifier: yc19555-HMO-CTIL
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

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

Interventions

Phenytoin DRUG

Rifampicin DRUG

Diclophenac DRUG

Fluconazole DRUG

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age range 20-50
• Absence of significant disease states

You may not qualify if:

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

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Organization

Jerusalem, Israel

Location

MeSH Terms

Interventions

Phenytoin; Rifampin; Diclofenac; Fluconazole

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Triazoles

Study Officials

• Yoseph Caraco, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 27, 2005
• Study Start: August 1, 1999
• Last Updated: October 29, 2008

Record last verified: 2008-10

Locations

IL (1)