Buprenorphine Disposition and CYP3A

Subjects will be studied during a maximum of seven occasions.

Study drugs are intravenous buprenorphine (0.025-0.2 mg infused over 1 hr) and sublingual buprenorphine (2-4 mg), with 1-3 week washout between sessions.

Sessions 1&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)

Sessions 3&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine

Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine

Sessions 6&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine

Inclusion criteria

Each subject must meet all of the following criteria:

• Male or non-pregnant female volunteer, 18-50 yr old
• Good general health with no known major medical conditions
• BMI < 33
• Provide informed consent

Exclusion criteria

Subjects will not be enrolled if any of the following criteria exist:

• Known history of liver or kidney disease
• Use of prescription or non-prescription medications, herbals or foods known to be metabolized by or affect CYP3A activity (this includes the use of oral contraceptives).
• Females who are pregnant or nursing
• Known history of drug or alcohol addiction (prior or present addiction or addiction treatment)
• Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential)