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Drug Interactions Between Silimarine and Darunavir/Ritonavir

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ClinicalTrials.gov Identifier: NCT01346982
Recruitment Status : Completed
First Posted : May 4, 2011
Last Update Posted : September 30, 2011
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
HIV Drug: Silimarine Phase 4

Detailed Description:

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Drug Interactions Between Silimarine And Darunavir/Ritonavir
Study Start Date : March 2011
Primary Completion Date : July 2011
Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Silimarine
darunavir + ritonavir + silimarine
Drug: Silimarine
darunavir/ritonavir 600/100 mg + silimarine (150 mg every 8 hours)

Outcome Measures

Primary Outcome Measures :
  1. Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of darunavir [ Time Frame: DAY 0, day 14 ]

Secondary Outcome Measures :
  1. Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of ritonavir [ Time Frame: DAY 0, day 14 ]
  2. Darunavir and ritonavir clearance (CL/F) [ Time Frame: DAY 0, day 14 ]
    Change from day 0 in Darunavir and ritonavir clearance at day 14

  3. Darunavir and ritonavir volume of distribution (V/F) [ Time Frame: DAY 0, day 14 ]
    Change from day 0 in Darunavir and ritonavir volume of distribution at day 14

  4. Darunavir and ritonavir elimination half-life (t1/2) of darunavir and ritonavir [ Time Frame: DAY 0, day 14 ]
  5. Darunavir and ritonavir trough concentration in plasma [ Time Frame: DAY 0, day 14 ]
  6. Adverse events and laboratory abnormalities [ Time Frame: DAY 0, 14, 28 ]
    Number of patients with adverse events and laboratory abnormalities grade 3 or 4

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01346982

Lluita contra la Sida Foundation, HIV Unit
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Fundacio Lluita Contra la SIDA
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
More Information

Responsible Party: Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier: NCT01346982     History of Changes
Other Study ID Numbers: SILIDAR
First Posted: May 4, 2011    Key Record Dates
Last Update Posted: September 30, 2011
Last Verified: September 2011

Keywords provided by Fundacio Lluita Contra la SIDA:

Additional relevant MeSH terms:
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors