Prediction of Drug Interactions With CYP2C9 Substrates
Information source: Hadassah Medical Organization
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Volunteers
Intervention: Phenytoin (Drug); Rifampicin (Drug); Diclophenac (Drug); Fluconazole (Drug)
Sponsored by: Hadassah Medical Organization
Official(s) and/or principal investigator(s):
Yoseph Caraco, MD, Principal Investigator, Affiliation: Hadassah Medical Organization
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
Official title: Prediction of Potential Drug Interaction With CYP2C9 Substrate by Using Phenytoin Metabolic Ratio as a Marker of Its Activity in-Vivo.
Study design: Other, Randomized, Double-Blind, Active Control, Crossover Assignment, Pharmacokinetics Study
Primary outcome: Phenytoin metabolic ratio prior to and following exposure to fluconazole, diclophenac and rifampicin.
Minimum age: 20 Years.
Maximum age: 50 Years.
- Age range 20-50
- Absence of significant disease states
- Known hypersensitivity to one of the drugs used in the study
- Significant disease states
- Regular use of drugs (including birth control pills)
Locations and Contacts
Hadassah Medical Organization, Jerusalem, Israel
Starting date: August 1999
Last updated: March 17, 2008