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.

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.

120 hours after warfarin dosing

Each of 10 participants received 2 treatments (warfarin, with or without rifampin), in randomly assigned order, separated by a minimum of 14 days. Participants presented for venous blood collection and were assessed for adverse events at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after warfarin dosing.