Efavirenz and Ritonavir on Human Brain P-Glycoprotein

Study Overview
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Brief Summary
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To determine the effects of ritonavir and efavirenz on the activity of P-glycoprotein in human brain.

Detailed Description
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Sequential crossover using tracer 11C-desmethylloperamide, a substrate for brain P-glycoprotein, and positron emission tomography (PET), administered after nothing (control), oral ritonavir (3d), and oral efavirenz (14d) with washout in between

Official Title
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Influence of Efavirenz and Ritonavir on Human Brain P-Glycoprotein Activity Using PET Imaging

Conditions
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Drug Effects

Intervention / Treatment
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* Drug: [11C] desmethyl-loperamide
* Other: Control - no pretreatment
* Drug: Oral ritonavir
* Drug: Oral efavirenz


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female, 18-40 yr old Good general health with no remarkable medical conditions BMI < 33 Provide informed consent Exclusion Criteria: Known history of liver or kidney disease History of major medical conditions HIV seropositive Fasting blood glucose > 110 mg/dl Family history of type 2 diabetes Use of prescription or non prescription medications, herbals or foods known to be metabolized by or altering P-glycoprotein or CYP3A activity (hormonal birth control medications are acceptable if alternative means of contraception are used) Females who are pregnant or nursing Females taking hormonal contraceptives who are unwilling to use alternative means of contraception Contraindications to MRI Contraindications to PET scanning

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>Session 1: Control (no pretreatment) - IV 10-14 mCi of [11C] desmethyl-loperamide (dLop) with PET/CT imaging | Drug: [11C] desmethyl-loperamide<br>* IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging<br>Other: Control - no pretreatment<br>* Session 1: IV administration of 10-14 mCi [11C] desmethyl-loperamide (dLop) with PET/CT imaging and brain MRI<br>|
| Active Comparator: Oral ritonavir<br>Session 2: Pretreatment with oral ritonavir for 3 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging | Drug: [11C] desmethyl-loperamide<br>* IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging<br>Drug: Oral ritonavir<br>* Session 2: Pretreatment with oral ritonavir for 3 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI<br>|
| Active Comparator: Oral efavirenz<br>Session 3: Pretreatment with oral efavirenz for 14 days followed by IV 10-14 mCi of [11C]dLop with PET/CT imaging | Drug: [11C] desmethyl-loperamide<br>* IV administration of 10-14 mCi of [11C] desmethyl-loperamide with PET/CT imaging<br>Drug: Oral efavirenz<br>* Session 3: Pretreatment with oral efavirenz for 14 days followed by IV administration of 10-14 mCi [11C]dLop with PET/CT imaging and brain MRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral [11C]dLop Distribution Volume |  | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET Imaging, Efavirenz, Ritonavir, [11C] desmethyl-loperamide, Healthy volunteers