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Prediction of Drug Interactions With CYP2C9 Substrates

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

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
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

Ages Eligible for Study:   20 Years to 50 Years   (Adult)
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
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Please refer to this study by its identifier: NCT00226538

Hadassah Medical Organization
Jerusalem, Israel
Sponsors and Collaborators
Hadassah Medical Organization
Principal Investigator: Yoseph Caraco, MD Hadassah Medical Organization
  More Information Identifier: NCT00226538     History of Changes
Other Study ID Numbers: yc19555-HMO-CTIL
Study First Received: September 12, 2005
Last Updated: October 28, 2008

Additional relevant MeSH terms:
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers processed this record on April 24, 2017