Identification and evaluation of endogenous markers for the assessment of CYP3A activity in female subjects using metabolomics
Eligibility for participation of this study will be determined from demographic information, medical history, physical examination, electrocardiogram(ECG) and clinical laboratory tests within 3 weeks before study drug administration. Subjects suitable for this study will be admitted to the Clinical Trials Center, Seoul National University Hospital on the day before dosing, and they will be overnight-fasted from 9 p.m. of Day -1. Urine collection is scheduled from 24 hours before midazolam administration to 24 hours after administration. Subjects will be dosed midazolam by intravenous around at 9 a.m. of Day 1. Subjects will perform scheduled procedures including clinical laboratory tests, electrocardiograms and pharmacokinetic samplings. Subjects will be discharged on Day 2 and visit the Clinical Trials Center for period 2, ketoconazole administration. After 3 days of ketoconazole administration, midazolam will be dosed with ketoconazole on Day 4 of period 2. Subjects will perform scheduled procedure and on period 3 rifampicin will be dosed for 9 days and on Day 10 of period 3 midazolam will be dosed with rifampicin. After subjects perform scheduled procedure, the study will be terminated 6-8 days after the end of period 3.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Midazolam 3 mg IV
ketoconazole 400 mg PO
Rifampicin 600 mg PO
Seoul National Universtiy Hospital
Seoul, South Korea
Metabolomic profile
endogenous metabolite profiles such as steroid
Time frame: -24--12h, -12-0h of every midazolam dosing
Pharmacokinetics
Cmax, AUClast of midazolam
Time frame: 0h, 10m, 20m, 30m, 45m, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h of every midazolam dosing
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