Disposition Effects of Cyclosporin on Buprenorphine

Subjects will be studied on four occasions in the Clinical Research Unit at Washington
University School of Medicine. Sessions and drugs are:

1. Intravenous buprenorphine

2. Sublingual buprenorphine

3. Cyclosporine, then intravenous buprenorphine. Subjects then take oral cyclosporine twice
daily, until

4. Sublingual buprenorphine; continue oral cyclosporine twice daily for 5 days

Inclusion Criteria:

- 18-50 yr old

- Good general health with no remarkable medical conditions

- BMI < 33

- Provide informed consent

Exclusion Criteria:

- Known history of liver or kidney disease

- Use of prescription or non prescription medications, herbals or foods known to be
metabolized by or affecting CYP3A

- Females who are pregnant or nursing

- Known history of drug or alcohol addiction (prior or present addiction or treatment
for addiction)

- Direct physical access to and routine handling of addicting drugs in the regular
course of duty (a routine exclusion from studies of drugs with addiction potential)