Buprenorphine Disposition and CYP3A

Study Overview
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Brief Summary
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To evaluate role of CYP3A in buprenorphine disposition and effect

Detailed Description
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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

Official Title
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Influence of CYP3A Modulation on Buprenorphine Disposition and Clinical Effects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Buprenorphine Control
* Drug: Buprenorphine + Rifampin
* Drug: Buprenorphine + Grapefruit juice
* Drug: Buprenorphine + Ketoconazole


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy males and non-pregnant females<br>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 | Drug: Buprenorphine Control<br>* Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)<br>Drug: Buprenorphine + Rifampin<br>* Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine<br>Drug: Buprenorphine + Grapefruit juice<br>* Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine<br>Drug: Buprenorphine + Ketoconazole<br>* Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Cmax of Buprenorphine |  | 96 hr | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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buprenorphine CYP3A