Official Title: “The Effects of Rifampin on the Pharmacokinetics of Warfarin in Healthy Volunteers.”

The purpose of this study is to determine the importance of uptake drug transporters in the drug disposition of warfarin. We predict that the elimination of warfarin will be decreased when co-dosed with an inhibitor of uptake drug transporters.

Study Type: Interventional

Study Design: Basic Science, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics/Dynamics Study

Study Primary Completion Date: March 2009

Intervention(s) in this Clinical Trial

• Drug: warfarin plus rifampin
  • warfarin 7.5mg po x 1; rifampin 600mg IV x 1
• Drug: warfarin
  • warfarin 7.5mg po x 1

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: warfarin plus rifampin
• Active Comparator: warfarin

Primary Measures

• Pharmacokinetics of warfarin dosed with and without rifampin.
  • Time Frame: Day 1
    Safety Issue?: No

Inclusion Criteria:

• Male or female 18-60 years of age;
• Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on history, physical exam and laboratory evaluations;
• BMI between 18.5 - 30 kg/m2;
• Taking no medications 2 weeks before and during the study enrollment, including drugs of abuse, prescription or OTC medications (except acetaminophen);
• Subjects able to maintain adequate birth control during the study independent of hormonal contraceptive use;
• Be able to provide written informed consent and comply with requirements of the study;
• Avoid eating grapefruit and drinking grapefruit juice from 7 days before the first study day until completion of the entire study;
• Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 6pm the night before a study day until completion of that study day;
• Avoidance of contact sports and/or other activities with significant risk of trauma injury for 7 days after each study day.
• Fast from food and beverages at least 8 hours prior to medication dosing;
• Be able to read, speak and understand English

Exclusion Criteria:

• Subjects on prescription or chronic over-the counter medications (including hormonal contraceptives);
• Subjects with known allergy to warfarin and/or rifampin;
• Subjects who are not homozygous for CYP2C9 *1 (known poor metabolizers).
• Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias;
• Subjects with liver failure or LFTs >2x upper limit of normal;
• Subjects with clinically significant elevations in INR, PT, PTT, SCr, BUN or other screening laboratory tests as determined by study physician;
• Subjects with Hct <30 mg/dL;
• Subjects with history of GI bleed or peptic ulcer disease;
• Subjects with a recent history of trauma;
• Subjects with a recent history of or upcoming plan of surgery;
• Subjects who smoke tobacco;
• Subjects with ongoing alcohol or illegal drug use;
• Subjects who are pregnant, lactating or attempting to conceive;
• Subjects unable to maintain adequate birth control during the study;
• Subjects unable to follow protocol instructions or protocol criteria.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

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

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

Leslie Z Benet, PhD Principal Investigator University of California, San Francisco  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00777855

Study ID Number: warfarin-6006

ClinicalTrials.gov Identifier: NCT00777855

Health Authority: United States: Institutional Review Board