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Prediction of Drug Interactions With CYP2C9 Substrates

This study has been completed.
Sponsor:
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT00226538
First received: September 12, 2005
Last updated: October 28, 2008
Last verified: October 2008
  Purpose

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 Intervention
Healthy Volunteers
Drug: Phenytoin
Drug: Rifampicin
Drug: Diclophenac
Drug: Fluconazole

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Official Title: Prediction of Potential Drug Interaction With CYP2C9 Substrate by Using Phenytoin Metabolic Ratio as a Marker of Its Activity in-Vivo.

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Phenytoin metabolic ratio prior to and following exposure to fluconazole, diclophenac and rifampicin.

Estimated Enrollment: 16
Study Start Date: August 1999
  Eligibility

Ages Eligible for Study:   20 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00226538

Locations
Israel
Hadassah Medical Organization
Jerusalem, Israel
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Yoseph Caraco, MD Hadassah Medical Organization
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00226538     History of Changes
Other Study ID Numbers: yc19555-HMO-CTIL
Study First Received: September 12, 2005
Last Updated: October 28, 2008
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Phenytoin
Anticonvulsants
Cardiovascular Agents
Central Nervous System Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on November 24, 2014