NCT00011635

The Effect of Milk Thistle on the Pharmacokinetics of Indinavir

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (planned)
• Sponsor: National Institutes of Health Clinical Center (CC) · NIH
• Sex: All
• Age: —
• Healthy volunteers: Accepted

Summary

Complementary and alternative medicines are widely used in the HIV-infected population. Recent data have shown serious drug interactions between certain complementary medicines and protease inhibitors. Silymarin (Milk thistle) is a commonly used dietary supplement in HIV-infected patients for treatment of hepatitis or as a hepato-protectant. Data are available suggesting that it may alter cytochrome P4503A4-mediated drug metabolism. To evaluate the effect of milk thistle on the protease inhibitor, indinavir (IDV), ten healthy subjects will receive IDV (Crixivan) alone and in combination with an over-the-counter silymarin preparation. IDV will initially be administered alone at a dose of 800 mg Q8H for four doses and serial samples will be collected for determination of IDV pharmacokinetics after the morning dose on day 2. Subjects will then initiate therapy will milk thistle using a standardized formulation and dose for three weeks after which subjects will then again take 4 doses of IDV and have serial samples collected for IDV plasma concentrations. There will then be a 11-day washout period with no drugs, after which IDV will again be given for 4 doses and samples will be collected evaluate the offset of the effects of milk thistle. To examine the effect of milk thistle on other CYP450 pathways, subjects will receive a single dose of caffeine and dextromethorphan and have urine collected before and after milk thistle, and after the washout period. Indinavir, caffeine, and dextromethorphan concentrations in plasma or urine will be determined using validated HPLC methods. Steady-state noncompartmental parameters of indinavir in the presence and absence of milk thistle will be determined. Pharmacokinetic parameters will be compared using ANOVA that will include factors for a period effect and a treatment effect. Statistical analyses will include calculation of the mean ratio of the AUC in the treatment phases compared to IDV alone and determination of 95% confidence intervals. This study will help define the drug interaction potential of complementary and alternative therapies in HIV-infected patients.

Detailed description

Complementary and alternative medicines are widely used in the HIV-infected population. Recent data have shown serious drug interactions between certain complementary medicines and protease inhibitors. Silymarin (Milk thistle) is a commonly used dietary supplement in HIV-infected patients for treatment of hepatitis or as a hepato-protectant. Data are available suggesting that it may alter cytochrome P4503A4-mediated drug metabolism. To evaluate the effect of milk thistle on the protease inhibitor, indinavir (IDV), ten healthy subjects will receive IDV (Crixivan) alone and in combination with an over-the-counter silymarin preparation. IDV will initially be administered alone at a dose of 800 mg Q8H for four doses and serial samples will be collected for determination of IDV pharmacokinetics after the morning dose on day 2. Subjects will then initiate therapy will milk thistle using a standardized formulation and dose for three weeks after which subjects will then again take 4 doses of IDV and have serial samples collected for IDV plasma concentrations. There will then be an 11-day washout period with no drugs, after which IDV will again be given for 4 doses and samples will be collected evaluate the offset of the effects of milk thistle. To examine the effect of milk thistle on other CYP450 pathways, subjects will receive a single dose of caffeine and dextromethorphan and have urine collected before and after milk thistle, and after the washout period. Indinavir, caffeine, and dextromethorphan concentrations in plasma or urine will be determined using validated HPLC methods. Steady-state noncompartmental parameters of indinavir in the presence and absence of milk thistle will be determined. Pharmacokinetic parameters will be compared using ANOVA that will include factors for a period effect and a treatment effect. Statistical analyses will include calculation of the mean ratio of the AUC in the treatment phases compared to IDV alone and determination of 95% confidence intervals. This study will help define the drug interaction potential of complementary and alternative therapies in HIV-infected patients.

Conditions

• HIV Infection
• Healthy

Interventions

Type	Name	Description
DRUG	Silymarin (milk thistle)

Timeline

• Start date: 2001-02-01
• Completion: 2001-06-01
• First posted: 2002-12-10
• Last updated: 2008-03-04

Locations

1 site across 1 country: United States