Fenofibrate의 생물학적동등성시험 표준지침서 작성을 위한 생체이용율시험 = Bioavailability Studies of fenofibrate for the Guidance of Bioequivalence

다국어 초록 (Multilingual Abstract)

Title : Bioavailability studies of fenofibrate for the guidance of bioequivalence
Purpose : To provide a standard protocol of fenofibrate for the guidance of bioequivalence
Results : A reversed phase high-performance liquid chromatographic method with detection 287 nm was developed and validated for the determination of fenofibrate in human plasma. Clofibric acid was used as internal standard. Calibration curves were linear in the concentration ranges of 0.2 16 ug/ml. Limit of quantitation was 0.2 ug/ml. The coefficient of variations of the intra-day and inter-day precision were below 15%. The coefficient of variations of the accuracy were below 15% in the concentration range of 0.2 16 ug/ml. A bioavailability study of fenofibrate was performed using the validated HPLC method. Eight healthy human male volunteers were orally administered 200 mg of fenofibrate capsule. Blood samples were withdrawn at designated times (1, 2, 3, 4, 5, 6, 7, 9, 12, 24, 48, 72 hrs). The plasma concentration of fenofibrate was determined using the validated HPLC method. The plasma concentration time profile of fenofibrate was analyzed using WinNonlin to calculate the following pharmacokinetic parameters: AUC, Cmax, Tmax, Ke, and ti/2. The bioavailability study of fenofibrate was repeated exactly the same way by two different laboratories to compare the study results among the three laboratories. The pharmacokinetic parameters among the three laboratories showed almost the same values. The mean values of AUC72hr, Cmax, Tmax, Ke, ti/2 were 107.83 ± 31.71 ug hr/ml, 3.81 ± 1.54ug/ml, 5.97 土 2.22 hr, 0.0307 ± 0.0055 1/hr, and 24.11 土 6.17 hr, respectively.
Conclusion : An HPLC method to determine fenofibrate in human plasma was developed and validated. Using this method, three separate bioavailability studies of fenofibrate were conducted by three different laboratories. Each laboratory used 8healthy human male volunteers and PK parameters were calculated. The PK parameters among the three laboratories showed comparable values. Therefore, the protocol used in the present bioavailability study can be used as a guidance for the bioequivalence study of fenofibrate.

국문 초록 (Abstract)

Ⅰ . 제 목
Fenofibrate의 생물학적 동등성시험 표준지침서 작성을 위한 생체이용율시험
Bioavailability studies of fenofibrate for the guidance of bioequivalence
Ⅱ. 연구개발의 목적 및 필요성
Fenofibrate에 대한 표준 생물학적동등성시험 지침 제시를 통한 생물학적동등성시험의 활성화 및 관리의 효율화
Ⅱ. 연구개발의 내용 및 범위
Fenofibric acid의 혈중농도 분석법의 validation을 통하여 표준분석조건을 확립하고，식약청에서 공고한 대조약으로 각 기관마다 건강한 성인 8명을 대상으로 순차적인 생체이용율시험을 실시하였다. 피험자의 건강진단, 투약, 채혈, 이상약물반응 발생의 예방 및 처치 둥은 세 기관 모두 순천향병원에서 담당의사인 권준택교수의 감독하에 실시하였고, 건강진단은 대한임상검사정도관리협회에 등록되어 정기적인 정도관리진단을 받고 있는 순천향병원소속 임상검사실(대한임상검사정도관리 협회 등록번호 : 97)에서 실시하였다. 약물동태 파라미터인 AUC, AUCco, 최고혈중농도(Cmax), 최고혈중농도 도달시간(Tmax), 소실속도상수(Ke) 및 반감기(t1/2) 등을 평가•검증하여 최종적인 fenofibrate의 표준 생물학적동등성 시험 지침서를 작성하였다.
...[중략]원문참조○ 연구목표 : Fenofibrate에 대한 표준 생물학적동등성시험 지침 제시를 통한 생물학적동등성시험의 활성 및 관리의 효율화
...[중략] 원문참조