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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
24
induction of CYP3A4 with one of three rifampicin doses (10, 20, 100 mg QD)
Clinical Pharmacology Trial Unit (CPTU), Karolinska University Hospital
Stockholm, Sweden
Change in 4beta-OHcholesterol
The primary objective of the study is to investigate whether the endogenous cholesterol metabolite 4β-hydroxycholesterol could be used as a marker for induction of CYP3A4. For this purpose the induction of 4β-hydroxycholesterol formation will be compared to the induction of quinine and midazolam metabolism.
Time frame: Directly before treatment with rifampicin and 14 days after the end of treatment with rifampicin
Ratio between midazolam AUC induced and midazolam AUC uninduced
Secondary aim of the study is to compare 4β-hydroxycholesterol as a biomarker for CYP3A4 compared to 6β-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.
Time frame: Before treatment with rifampicin and after 14 days of treatment with rifampicin
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