Drug Interactions Between Silimarine and Darunavir/Ritonavir

Drug Interactions Between Silimarine And Darunavir/Ritonavir

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

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Silimarine

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Lluita contra la Sida Foundation, HIV Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Collaborators: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; IrsiCaixa

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: April 18, 2011
• First Submitted That Met QC Criteria: May 3, 2011
• First Posted (Estimate): May 4, 2011

Study Record Updates

• Last Update Posted (Actual): November 14, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Darunavir; interaction; Silimarine
• Other Study ID Numbers: SILIDAR; 2010-021159-25