HIV
Conditions
Keywords
Darunavir, Silimarine, interaction
Brief summary
This is a clinical trial to characterize drug interactions between silimarine and the protease inhibitor darunavir/ritonavir.
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.
Interventions
DRUGSilimarine
darunavir/ritonavir 600/100 mg + silimarine (150 mg every 8 hours)
Sponsors
IrsiCaixa
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of darunavir | DAY 0, day 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Darunavir and ritonavir clearance (CL/F) | DAY 0, day 14 | Change from day 0 in Darunavir and ritonavir clearance at day 14 |
| Darunavir and ritonavir volume of distribution (V/F) | DAY 0, day 14 | Change from day 0 in Darunavir and ritonavir volume of distribution at day 14 |
| Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of ritonavir | DAY 0, day 14 | — |
| Darunavir and ritonavir trough concentration in plasma | DAY 0, day 14 | — |
| Adverse events and laboratory abnormalities | DAY 0, 14, 28 | Number of patients with adverse events and laboratory abnormalities grade 3 or 4 |
| Darunavir and ritonavir elimination half-life (t1/2) of darunavir and ritonavir | DAY 0, day 14 | — |
Countries
Spain
Outcome results
None listed