Drug Interaction Study of Rifampin and Warfarin in Healthy Volunteers.

• ClinicalTrials.gov Identifier: NCT00777855
• Recruitment Status: Completed
• First Posted: October 22, 2008
• Results First Posted: July 17, 2013
• Last Update Posted: July 17, 2013
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: warfarin plus rifampin; Drug: warfarin	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Effects of Rifampin on the Pharmacokinetics of Warfarin in Healthy Volunteers.
• Study Start Date: November 2008
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: March 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: warfarin then warfarin plus rifampin	Drug: warfarin plus rifampin; warfarin 7.5mg po x 1; rifampin 600mg IV x 1; Drug: warfarin; warfarin 7.5mg po x 1

Outcome Measures

Primary Outcome Measures :

1. S- and R- Enantiomers of Warfarin (S-warfarin and R-warfarin) Area Under the Plasma Concentration-time Curve (AUC) From 0 to 12 Hours. [ Time Frame: 0-12 hours after warfarin dosing ]
   Uptake effects on warfarin pharmacokinetics during time period of hepatic organic anion-transporting polypeptide (OATP) inhibition by rifampin. Blood collection 1, 2, 4, 6, 8, and 12 hours after warfarin dosing.

Secondary Outcome Measures :

1. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity of S-warfarin and R-warfarin [ Time Frame: 0-120 hours after warfarin dosing ]
   Analysis of all concentration-time data. Blood collection 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after warfarin dosing.
2. Maximum Plasma Concentration (Cmax) of S-warfarin and R-warfarin [ Time Frame: 0-120 hours after warfarin dosing ]
   Blood collection 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after warfarin dosing.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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 over-the-counter (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 cytochrome P450 2C9 (CYP2C9 *1) (known poor metabolizers).
• Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias;
• Subjects with liver failure or liver function test (LFT) results >2x upper limit of normal;
• Subjects with clinically significant elevations in international normalized ratio (INR), prothrombin (PT), prothrombin time (PTT), serum creatinine (SCr), blood urea nitrogen (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.

Contacts and Locations

Locations

United States, California

UCSF Medical Center

San Francisco, California, United States, 94112

Sponsors and Collaborators

University of California, San Francisco

Investigators

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

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00777855 History of Changes
• Other Study ID Numbers: warfarin-6006
• First Posted: October 22, 2008
• Results First Posted: July 17, 2013
• Last Update Posted: July 17, 2013
• Last Verified: May 2013

Keywords provided by University of California, San Francisco:

warfarin; pharmacokinetics; drug transporter; healthy volunteer; drug interaction; rifampin

Additional relevant MeSH terms:

Rifampin; Warfarin; Anticoagulants; 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