HepaRG 세포를 이용한 Bosentan 약물의 CYP450 효소활성 측정

• 영문명: Measurement of CYP450 Enzymes Activity of Bosentan in HepaRG Cell
• 발행기관: 대한약학회
• 저자명: 한경문 정정아 신지순 차혜진 배영지 김현욱 김영훈 성원근 강호일
• 간행물 정보: 『약학회지』제58권 제4호 (2014년), 255~261쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2014.08.31

영문 초록

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metab- olism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are sev-eral limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 µM omeprazole, 2C9 and 2C19: 10 µM rifampin, 3A4: 10, 25, 50 µM rifampin) at 37 o C, 5 % CO2 in a humidified atmosphere. This study was to eval-uate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction abil-ity of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the Cmax (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

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