To investigate the effect of rifampicin and febuxostat on pharmacokinetics of methotrexate in healthy volunteers

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