Buprenorphine Disposition and CYP3A

The Washington University

Status: Completed

Conditions: Healthy

Treatments: Drug: Buprenorphine + Rifampin; Drug: Buprenorphine + Grapefruit juice; Drug: Buprenorphine Control; Drug: Buprenorphine + Ketoconazole

Study type: Interventional

Funder types: Other

Identifiers

NCT01576575

201104146

Details and patient eligibility

About

To evaluate role of CYP3A in buprenorphine disposition and effect

Full 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

Enrollment: 21 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Each subject must meet all of the following criteria:

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

Exclusion criteria

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

1. Known history of liver or kidney disease
2. 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).
3. Females who are pregnant or nursing
4. Known history of drug or alcohol addiction (prior or present addiction or addiction treatment)
5. 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)

Trial design

21 participants in 1 patient group

Healthy males and non-pregnant females

Experimental group

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

Treatment:

Drug: Buprenorphine + Grapefruit juice

Drug: Buprenorphine + Ketoconazole

Drug: Buprenorphine Control

Drug: Buprenorphine + Rifampin