Drug Interaction
Conditions
Brief summary
To investigate the effect of rifampicin and febuxostat on pharmacokinetics of methotrexate in healthy volunteers
Interventions
DRUGRifampicin Sodium
Co-administration of methotrexate and rifampicin
Methotrexate oral administration alone
Co-administration of methotrexate and febuxostat
Sponsors
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 19 to 50, healthy male subjects (at screening) * Body weight between 50.0 kg - 90.0 kg, BMI between 18.0 - 30.0 kg/m2 * Subject who totally understand the progress of this clinical trials, make decision by his free will, and signed a consent form to follow the progress
Exclusion criteria
* Subject who has a past or present history of any diseases (eg. liver, kidney, neurology, immunology, pulmonary, endocrine, hematology, oncology, cardiology, mental disorder) * Subject who had GI tract disease (Crohn's disease, ulcer, acute or chronic pancreatitis) or surgery (appendectomy, hernioplasty are excluded) * Serum AST(SGOT), ALT(SGPT), total bilirubin \>1.5 times upper limit of normal range, MDRD eGFR \< 60mL/min/1.73m2, WBC count \< 3,500 /uL, SBP \< 90 mmHg or \> 150 mmHg, DBP \< 50 mmHg or \>100 mmHg * Subject who had galactose intolerance, Lapplactase deficiency or glucose-galactose malabsorption * Subject who had received drugs inhibiting or inducing metabolic enzymes/transporters such as barbiturates, statins, digoxin in 3 months * Subject who had taken St.John's wort and food including grapefruit in 2 weeks * Smoking in 3 months * Subject who had whole blood donation in 2 months, or component blood donation in 1 month or transfusion in 1 month currently
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare Cmax of methotrexate | pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1) | Compare the maximum concentration (Cmax), area under the plasma concentration-time curve to last measurable time point (AUClast) and area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of methotrexate |
| Compare AUClast of methotrexate | pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1) | Compare the area under the plasma concentration-time curve to from 0 to last measurable time point (AUClast) of methotrexate |
| Compare AUCinf of methotrexate | pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1) | Compare area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of methotrexate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare Cmax of 7-hydroxy methotrexate | pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1) | Compare the maximum concentration (Cmax) of 7-hydroxy methotrexate |
| Compare AUClast of 7-hydroxy methotrexate | pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1) | Compare area under the plasma concentration-time curve to last measurable time point (AUClast) of 7-hydroxy methotrexate |
| Compare AUCinf of 7-hydroxy methotrexate | pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1) | Compare area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of 7-hydroxy methotrexate |
Countries
South Korea
Outcome results
None listed