Conditions: Healthy
Keywords: buprenorphine CYP3A
Allocation:  | Intervention model: SEQUENTIAL
Enrollment: 21
Healthy volunteers: yes

Brief summary:
To evaluate role of CYP3A in buprenorphine disposition and effect

Detailed description:
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

Arms:
arm 1: 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

Interventions: intervention 1: Buprenorphine Control intervention 2: Buprenorphine + Rifampin intervention 3: Buprenorphine + Grapefruit juice intervention 4: Buprenorphine + Ketoconazole
Intervention descriptions: intervention 1: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) intervention 2: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine intervention 3: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine intervention 4: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine

Protocol document: