Determine the Effects of Gene Differences and Voriconazole on Enzyme CYP2B6 Activity in the Liver in Healthy Volunteers

The investigators will test the hypothesis that CYP2B6 genetic variants that show effects in vitro also influence the in vivo activity of CYP2B6 and its responsiveness to metabolic inhibition, using the metabolism of efavirenz (100 mg dose) as a marker of activity. The metabolism and pharmacokinetics of efavirenz will be determined in a total of 60 healthy volunteers with CYP2B6*1/*1, CYP2B6*1*6 and CYP2B6*6*6 at baseline (control) and after pretreatment with voriconazole.

Inclusion criteria

• Male or female subject between 18 and 55 years of age.
• Healthy individuals without any significant medical conditions as determined by a screening performed at University.
• Adherence to the study dietary and medication restrictions.
• Willingness to refrain from smoking or use of tobacco or marijuana one week before the start of the study and until completion of the study which will be a total of 17 days.
• Ability to commit the time requested for this study.

Exclusion criteria

• Underweight (weighs less than 50kg or 110lb) or over weight [body mass index (BMI) greater than 32].
• Drug or alcohol abuse (more than 3 alcoholic drinks per day on a regular basis).
• History of intolerance or allergic reaction (e.g. rash) to efavirenz and/or voriconazole.
• Significant health conditions such heart, gastrointestinal disorders, liver, or kidney diseases that may be exacerbated during the course of the study.
• History or current psychiatric illness (e.g. depression, anxiety, or nervousness).
• History or current eye sight disturbances (e.g. blurred vision).
• Serious infection within the last 2 weeks.
• Blood donation within the past two months.
• Screening results that do not fall in a healthy range.
• Regularly taking prescriptions (except hormonal agents, e.g. oral contraceptives), over-the-counter, herbal or dietary supplements, and alternative medications and are unable or unwilling to stop taking them one week before and during the study periods.
• Female with a positive pregnancy test.
• Female breastfeeding.
• Females of child-bearing potential who are unable or unwilling to either practice abstinence or use appropriate birth control up until the study completion, which will take a total of 17 days.
• Participation in a research study involving intensive blood sampling and/or have use study drugs in the last two months.
• Employed or student under supervision of any of the investigators of this study.
• Inability to state a good understanding of this study including risks and requirements, and inability to follow the rules of this study.