Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00011635
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2001-02-24
Brief Title:
The Effect of Milk Thistle on the Pharmacokinetics of Indinavir
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
The Effect of Milk Thistle on the Pharmacokinetics of Indinavir
Status:
COMPLETED
Status Verified Date:
2000-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-CC-0054 | None | None | None |