Drug-Drug Interaction Between Rifampin and Fluvastatin
Condition: Drug-drug Interaction
Intervention: rifampin IV; Rifadin 300Mg Capsule; Fluvastatin 20 MG
Intervention description: A 30-min intravenous infusion of rifampin 600mg in 10ml Normal Saline will be used to inhibit hepatic OATP1B1 transporters.; Rifadin 600mg by mouth as two 300mg rifadin capsules; one oral dose of fluvastatin (Lescol ) 20mg capsule
Intervention MeSH terms: Rifampin
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This study is a two arm, randomized, open label, crossover, clinical trial. Arm 1 will be conducted in normal healthy volunteers; Arm 2 will be conducted in hepatically induced (by oral rifampin) healthy volunteers.
Masking: None (Open Label)
Masking description: No masking will be employed because it is very difficult to mask the effects of rifampin (range discoloration) on subjects.
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: drug-drug interaction; statin; rifampin

Summary:

      The effect of organic anion transporting polypeptide 1B1 (OATP1B1) transporter inhibition at
      clinical doses of fluvastatin, a biopharmaceutics drug disposition classification system
      (BDDCS) class 1 drug, has not been studied to date. A single dose of IV rifampin can be used
      as model OATP1B1 inhibitor to evaluate the significance of OATP1B1 transporter effects on
      fluvastatin disposition. A preinduction regimen of oral rifampin followed by a single IV
      infusion of rifampin can be used to evaluate the combined effects of enzyme induction and
      OATP1B1 transporter inhibition on fluvastatin disposition. A two arm, randomized, open label,
      crossover clinical study in healthy, volunteers will be conducted to evaluate the effects of
      IV rifampin on fluvastatin disposition in both hepatically induced and uninduced subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male or female, ages 18-65 years old, with no current medical conditions or
             active diagnoses as determined by the study doctor based on history, physical exam,
             and laboratory evaluations.

          2. Subjects who take no other medications two weeks prior to the study and during the
             time course of the study including prescription medications, over-the-counter
             medications, dietary supplements, or drugs of abuse.

          3. Subjects able to maintain adequate birth control during the study independent of
             hormonal contraceptives (including hormonal intrauterine devices (IUDs)). Adequate
             methods of contraception include use of condoms and copper IUDs.

          4. Subjects able to abstain from grapefruit, grapefruit juice, oranges, orange juice,
             caffeinated beverages and/or alcoholic beverages from 7am the day before the study to
             completion of that study day.

          5. Participants determined to have normal liver and kidney function as measured at
             baseline ( alanine aminotransferase (ALT): ≤ 2x upper level of normal (ULN), aspartate
             aminotransferase (AST): ≤ 2x ULN, serum creatinine (SCr): ≤ 1.5x ULN, T. Bili:
             0.1-1.2mg/dL, Albumin: 3.4 - 4.7 mg/dL).

          6. BMI between 18.0 - 30 kg/m2 o Subjects capable of fasting from food and beverages at
             least 8 hours prior to medication dosing.

          7. Be able to read, speak, and understand English.

          8. Subjects capable of providing informed consent and completing the requirements of the
             study.

        Exclusion Criteria:

          1. Subjects with active medical problems

          2. Subjects on chronic prescription or over the counter (OTC) medication that cannot be
             stopped 2 weeks prior to and during the study.

          3. Subjects incapable of multiple blood draws (HCT < 30mg/dL)

          4. Subjects with a history of rhabdomyolysis

          5. Subjects with a history of drug-related myalgias

          6. Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias

          7. Subjects with a history of GI bleed or peptic ulcer disease

          8. Subjects who smoke tobacco or have ongoing alcohol or illegal drug use

          9. Subjects who are pregnant, lactating, or trying to conceive during the study period

         10. Subjects allergic to fluvastatin or rifampin or any known component of the medications

         11. Anyone who in the opinion of the study investigators is unable to do the study