페룰산의 약물동태 및 간내 이행 = Pharmacokinetics and Hepatic Uptake of Ferulic Acid

다국어 초록 (Multilingual Abstract)

Ferulic acid, a compound isolated from herbs, has a big potential to be developed into a useful drug for the treatment of cardiovascular disease. Ferulic acid is effective at preventing cancer induced and reducing oxidative stress. but its pharmacokinetics and hepatic uptake have almost not been reported. Thus present study was to investigate the pharmacokinetics of ferulic acid after i.v administration, and to analyze in vivo hepatic uptake of ferulic acid. We developed a convenient HPLC methods using UV/VIS detector to assay ferulic acid in the biological fluids. Plasma concentration-time profiles of ferulic acid were determined after i.v. administration at a dose of 2 mg/kg and 10 mg/kg, respectively. Moreover, tissue concentration and the excreted amount into bile or urine were determined. Ferulic acid were rapidly disappeared from the blood circulation by 15 min after its i.v. bolus injection, followed by a slow disappearance by 1 hr. The half-lives at the distributive phase (t1/2α) and post-distributive phase (t1/2β) were 1.1-1.4 min and 5-7 min, respectively. Ferulic acid was rapidly eliminated during 30 min in the bile and 12 hr in the urine. Of the various tissues tested, ferulic acid was mainly distributed in the liver, kidney and L.intestine after i.v. administration. The plasma and liver concentration of ferulic acid were determined after i.v. bolus administration at a dose of 10 mg/kg in rats and then the hepatic uptake clearance (CLuptake,in vivo) was calculated from the slope of linear range over 3 min. The hepatic uptake clearance of ferulic acid was 0.0862 ml/min/g liver.

목차 (Table of Contents)

• Ⅰ. 서론 1
• Ⅱ. 연구 방법 2
• 1. 실험 재료 2
• 1.1. 시약 2
• 1.2. 실험 기기 2
• 1.3. 실험 동물 3
• 2. Ferulic acid의 HPLC 분석조건 4
• 2.1. UV 흡수파장의 검토 4
• 2.2. 이동상 용매 선택 4
• 2.3. 컬럼의 선택 4
• 2.4. 추출 용매의 선택 4
• 2.5. 내부 표준물질(IS)의 선택 5
• 2.6. HPLC 분석조건의 검증(validation) 5
• 3. 흰쥐에서 ferulic acid의 약물동태학적 분석을 위한 동물실험 6
• 3.1. 흰쥐에서 ferulic acid의 정맥투여 후 혈장 채취 6
• 3.2. 흰쥐에서 ferulic acid의 정맥투여 후 담즙 및 요의 채취 6
• 3.3. 조직분포 6
• 3.4. 혈장 중 ferulic acid의 농도 정량 7
• 3.5. 혈장 중 ferulic acid 농도의 약물동태학적 해석 10
• 3.5.1. 정맥주사 후 속도론적 파라미터 산출 10
• 3.5.2. 모델 비의존적 해석 12
• 4. Ferulic acid의 in vivo hepatic uptake 실험 13
• 4.1. Ferulic acid의 정맥투여 후 혈장 및 간 채취 13
• 4.2. 혈장 및 간조직중 ferulic acid 농도 정량 13
• 4.3. Ferulic acid의 간 내 유입 클리어런스의 산출 14
• Ⅲ. 결과 및 고찰 16
• 1. 흰쥐에서 HPLC 분석법의 검증(validation) 16
• 2. Ferulic acid 동물실험 20
• 2.1. 흰쥐에 ferulic acid의 정맥투여 후 체내동태 비교 20
• 2.2. 흰쥐에서 ferulic acid의 담즙 배설 23
• 2.3. 흰쥐에서 ferulic acid의 요 중 배설 26
• 2.4. 흰쥐에서 ferulic acid의 조직분포 29
• 3. Ferulic acid의 in vivo hepatic uptake study 32
• Ⅳ. 결론 36
• Ⅴ. 참고문헌 38