Earticle

초록

영어

Highly variable drugs (within-subject variability greater than 30%) have been difficult to meet current regulatory acceptance criteria using a reasonable number of study subjects. In this study, we reviewed previous studies presenting alternative approaches for bioequivalence evaluation of highly variable drugs, and focused on an approach for widening the bioequivalence acceptance limits using within-subject variability. We discussed the suggested five solutions for highly variable drug including the deletion of Cmax of the bioequivalence criteria, direct expansion of bioequivalence limit, multiple dose studies in steady state, bioequivalence assessment on the metabolite, add-on study, and widening the bioequivalence acceptance limits based on reference variability. The methods for widening of bioequivalence limits based on reference variability are scaled average bioequivalence containing within-subject variability on reference drug (σWR), population bioequivalence derived from total variability on reference drug (σTR) and test drug (σTT), and individual bioequivalence derived from subject by formulation interaction variability (σD) and within subject variability on reference drug (σWR) and test drug (σTR). To apply these methods, the switching variability (σ0) will have to be set by the regulatory authorities. The proposals of bioequivalence evaluation approach for the highly variable in Korea are presented for both of new drug and reevaluation drug.

목차

Abstract
 개체 변이가 큰 약물 (highly variable drug)
 생물학적동등성시험 관련 변이성(variation)
 Highly variable drug의 일반생동기준을 만족하기 위해 필요한 지원자 수
 국내·외 highly variable drug의생동성 기준 조사
 국제적으로 제시되는 highly variable drug 특별생동기준
  생물학적동등성 비교평가항목인 Cmax의 삭제
  생물학적동등성 비교평가항목인 Cmax의 생동 기준 (BElimit)의 단순 확장
  반복투여를 통한 정상상태 (steady state)에서의 시험
  약물의 대사체 (metabolite) 측정을 통한 시험
  부가 시험 (add-on study)을 통한 시험
  대조약의 변이성 (variability)를 고려한 생동 기준 (BE limit)의 확장
 BE limit 확장의 위험성 및 극복 방안
 국내 적용 목적으로 한 highly variable drug의 특별생동기준(안)
  새로운 약물 또는 새로운 제제의 허가를 위한 HVD 특별생동기준(안)
  약효 재평가를 위한 HVD 특별생동기준(안)
 결론
 참고문헌

키워드

저자

• 백인환 [ In-hwan Baek | 충남대학교 약학대학 임상약학 연구실 ]
• 성수현 [ Soo-hyeon Seong | 충남대학교 약학대학 임상약학 연구실 ]
• 권광일 [ Kwang-il Kwon | 충남대학교 약학대학 임상약학 연구실 ] Corresponding author

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국임상약학회지 [Korean Journal of Clinical Pharmacy]

• 간기

  계간

• pISSN

  1226-6051

• 수록기간

  1991~2026

• 등재여부

  KCI 등재

• 십진분류

  KDC 518 DDC 615