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

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.

Study Type: Interventional

Study Design: Other, Randomized, Double-Blind, Active Control, Crossover Assignment, Pharmacokinetics Study

Intervention(s) in this Clinical Trial

• Drug: Phenytoin
• Drug: Rifampicin
• Drug: Diclophenac
• Drug: Fluconazole

Primary Measures

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

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Hadassah Medical Organization

Overall Clinical Trial Officials and Contacts

Yoseph Caraco, MD Principal Investigator Hadassah Medical Organization  

Information obtained from ClinicalTrials.gov on August 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00226538

Study ID Number: yc19555-HMO-CTIL

ClinicalTrials.gov Identifier: NCT00226538

Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration