CYP3A4 Induction and Mineral Homeostasis

Healthy volunteers will receive one of six interventions for 14 days (determined by
randomization):a). 200 mL of water once a day; b) rifampin 600 mg once a day; c) 200 mL of
grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days; d)
clarithromycin 250 mg twice a day; f) clarithromycin 250 mg twice a day plus rifampin 600 mg
once a day.

Inclusion Criteria:

- Subjects with no history of significant medical conditions including cardiac,
pulmonary, gastrointestinal, or renal disease, HIV, diabetes mellitus or Hepatitis B
or C

- Subjects will be males or females 18-60 years of age

- Subjects must read and understand English

- Subjects must be able to provide informed consent

- Subjects must be willing to avoid prescription medications, OTC drugs, dietary
supplements and foods that are known to modulate CYP3A4 expression or activity

- Subjects must be willing to maintain a consistent consumption of calcium and Vitamin D
during the study and maintain a daily logbook of their dietary consumption

- Women not currently pregnant or lactating. In addition, women participants of
childbearing age must be willing to utilize a barrier method of birth control
(sterilization will be acceptable)

- Subjects will have no known allergies to the study drugs to be used

- Subject's corrected QTc interval obtained by electrocardiogram will be ≤ 430 ms in men
or ≤ 450 ms in women

Exclusion Criteria:

- Subjects with any significant chronic medical condition, including cardiac, pulmonary,
gastrointestinal, or renal disease, HIV, diabetes mellitus or Hepatitis B or C

- Subjects less than 18 or greater than 60 years of age

- Subjects unable to read and understand English

- Subjects unable to provide informed consent

- Subjects unable to avoid prescription medications, OTC drugs, dietary supplements and
foods that are known to modulate CYP3A4 expression or activity

- Subjects not willing to maintain a consistent consumption of calcium and Vitamin D
during the study and maintain a daily logbook of their dietary consumption

- Women who are pregnant or lactating and women participants of childbearing age not
willing to utilize a barrier method of birth control (sterilization will be
acceptable)

- Subjects with allergies to rifampin, clarithromycin or grapefruit juice

- Potential participants will be excluded if they are concurrently participating in
another research study

- Subjects with corrected QTc interval > 430 ms in men or > 450 ms in women on
electrocardiogram