CYP3A4 Induction Clinical Trial
Official title:
Induction of Drug Metabolism by Rifampicin to Compare the Endogenous Biomarker 4beta-OHcholesterol With the Probe Drug Midazolam as Quantitative Markers for Cytochrome P450 3A4 Induction
| Verified date | May 2011 |
| Source | Karolinska University Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Sweden: Medical Products Agency |
| Study type | Interventional |
The objectives of this study are:
- To investigate if the endogenous cholesterol metabolite, 4beta-OHcholesterol could be
used as a marker for induction of cytochrome P450 (CYP) 3A4.
- To compare 4beta-OHcholesterol with midazolam as a marker for induction of CYP3A4.
| Status | Completed |
| Enrollment | 24 |
| Est. completion date | July 2011 |
| Est. primary completion date | July 2011 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Females and males. 2. Age of 18 and above. 3. Caucasians. 4. Healthy as assessed by medical history and examination by principal investigator or delegated personnel. 5. Accept to refrain from herbal drugs, natural preparations, and grapefruit juice 48 hours before and during the study period. 6. Accept to completely refrain from alcohol during day -1 to 1 and R14-R16. During the rest of the study moderate alcohol use is permitted (equal to 1 glass of wine or 1 beer per day). 7. Women of childbearing age should accept using a reliable barrier contraceptive method throughout the study. 8. Women of childbearing age should have a negative pregnancy test at the screening visit. 9. Capable of following given instructions. 10. Has given written informed consent after receiving both oral and written study information. Exclusion Criteria: 1. Predisposal to allergic drug reactions. 2. Anamnestic and/or visual signs of infection. 3. Women are not allowed to use oral hormone-based contraceptives 2 weeks before start of study and during the study. 4. Participation in another study within one month before entering the present study. 5. Intake of any other drug that can influence the enzyme activity of CYP3A4. 6. Pregnancy. 7. Breast-feeding. 8. A history of liver disease. |
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
| Country | Name | City | State |
|---|---|---|---|
| Sweden | Clinical Pharmacology Trial Unit (CPTU), Karolinska University Hospital | Stockholm |
| Lead Sponsor | Collaborator |
|---|---|
| Karolinska University Hospital | AstraZeneca |
Sweden,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in 4beta-OHcholesterol | The primary objective of the study is to investigate whether the endogenous cholesterol metabolite 4ß-hydroxycholesterol could be used as a marker for induction of CYP3A4. For this purpose the induction of 4ß-hydroxycholesterol formation will be compared to the induction of quinine and midazolam metabolism. | Directly before treatment with rifampicin and 14 days after the end of treatment with rifampicin | No |
| Secondary | Ratio between midazolam AUC induced and midazolam AUC uninduced | Secondary aim of the study is to compare 4ß-hydroxycholesterol as a biomarker for CYP3A4 compared to 6ß-hydroxycortisol/cortisol ratio, which sometimes is used as a marker for CYP3A4 induction. Another secondary aim is to relate our estimations of CYP3A4-expression to measured levels of 25-OH-vitamin D. |
Before treatment with rifampicin and after 14 days of treatment with rifampicin | No |