Drug Interactions Between Silimarine and Darunavir/Ritonavir

Study Overview
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Brief Summary
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This is a clinical trial to characterize drug interactions between silimarine and the protease inhibitor darunavir/ritonavir.

Detailed Description
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The silimarine is the main component of milk thistle (Sylibum marianum), a medicinal herb which, due to its attributed hepatoprotective properties, is widely used by HIV infected patients 15 patients on stable antiretroviral therapy including darunavir/ritonavir 600/100 mg twice a day during four weeks will be enrolled. After their inclusion in the study, patients will receive treatment with silimarine (150 mg every 8 hours) from day 1 until two weeks later (day 14). On days 0 and 14, blood samples will be drawn immediately before and 1, 2, 4, 6, 8, 10 and 12 hours after the administration of darunavir/ritonavir, and darunavir and ritonavir concentrations in plasma will be determined by high performance liquid chromatography using a validated method.

Official Title
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Drug Interactions Between Silimarine And Darunavir/Ritonavir

Conditions
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HIV

Intervention / Treatment
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* Drug: Silimarine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients receiving antiretroviral therapy containing darunavir / ritonavir at the approved dose of 600/100 mg twice daily for at least 4 weeks HIV viral load in plasma <50 copies / mL Absence of acute infections and / or tumors in the three months prior to inclusion. Subject able to follow the treatment period, without suspicion of poor adherence in previous antiretroviral treatments. Exclusion Criteria: Any clinical or historical observation that could interfere with the pharmacokinetics of medications, such as gastrointestinal illness or surgery (except for herniotomy and appendectomy), changes in the composition of plasma proteins, some indication of hepatic or renal dysfunction. Active alcohol consumption (> 50 g / day) or illicit drugs (except cannabis).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Silimarine<br>darunavir + ritonavir + silimarine | Drug: Silimarine<br>* darunavir/ritonavir 600/100 mg + silimarine (150 mg every 8 hours)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of darunavir |  | DAY 0, day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of ritonavir |  | DAY 0, day 14 | 
| Darunavir and ritonavir clearance (CL/F) | Change from day 0 in Darunavir and ritonavir clearance at day 14 | DAY 0, day 14 | 
| Darunavir and ritonavir volume of distribution (V/F) | Change from day 0 in Darunavir and ritonavir volume of distribution at day 14 | DAY 0, day 14 | 
| Darunavir and ritonavir elimination half-life (t1/2) of darunavir and ritonavir |  | DAY 0, day 14 | 
| Darunavir and ritonavir trough concentration in plasma |  | DAY 0, day 14 | 
| Adverse events and laboratory abnormalities | Number of patients with adverse events and laboratory abnormalities grade 3 or 4 | DAY 0, 14, 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Darunavir, Silimarine, interaction