비임상시험 ADME

Drug metabolism and transport based ADME Service

 

 
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비임상 ADME 서비스란?

ADME란?

ADME는 “Absorption(흡수), Distribution(분포), Metabolism(대사), Excretion(배설)”의 약자로서,
하나의 약물이 생체 내 목표하는 장기에 이르기까지의 처리되는 과정입니다.
본 검사는 약물의 안전성, 유효성 평가 및 인증에 필요한 ADME 시험항목 서비스를 제공합니다.
  • 후보물질의 신약화 가능성을 평가 지원
  • 개발 기간 단축 및 신약 성공 가능성을 높임

SPMED의 비임상 ADME 서비스는?

  • US FDA에서 권고하는 비임상 ADME 시험항목 서비스 가능
  • 의뢰자 요청에 따른 서비스 항목 개발 가능
  • 약물 대사 및 약물 수송체 관련하여 광범위한 ADME 기반기술 보유
  • 약물대사/수송체, 약물동태 관련 국내외 연구자와의 다양한 네트워크
  • 국내외 다수의 신약 개발 전임상 및 임상 과제를 수행한 연구진
  • 인제의대 약물유전체연구센터의 최상급 연구시설 및 장비 사용

비임상 ADME 분석 서비스 리스트

분류 항목
Permeability test Cell Permeability Test
Metabolism study Metabolic Stability
Metabolite Profiling & Identification
Reaction Phenotyping
Transport study Uptake Transport Study
Efflux Transport Study
Cryopreserved Hepatocytes Uptake
Hepatic Excretion by Sandwich Cultured Hepatocytes
Drug-Drug Interaction study Enzyme Inhibition
Time-dependent Inhibition
Transporter Inhibition
Enzyme / Transporter Induction

비임상 ADME 분석 서비스

Permeability test

  • Drug absorption
    Caco-2 cell permeability test
  • Hepatic excretion
    Cryopreserved hepatocytes uptake, Sandwich cultured hepatocytes

In vitro Metabolism study

  • Protein binding
    Plasma protein binding, microsomal binding: Equilibrium dialysis
  • Metabolic stability
    metabolic stability (hepatocytes, microsomes, S9)
    plasma stability
    Species comparison (mouse, rat, dog, monkey, human)
  • Reaction Phenotyping
    Reaction phenotyping and kinetics : P450s, UGTs, non-CYP Phase I
    Enzyme systems: recombinant enzymes, microsome, S9, hepatocytes
    Kinetic studies (Km, Vmax, intrinsic clearance)
    Pharmacogenetics study (CYP2C19*10, CYP2D6*10B, CYP4F2*3)
  • Met ID
    Metabolite profiling and Met ID

In vitro Transporter study

  • Identification of transport system
    Vesicle-based transporter assay
    Uptake transport screening in overexpressing cells or oocytes(OCTs, OATs, OATPs, MATEs, NTCP)
    Efflux transport screening in overexpressing cells (MDR1, BCRP, MRP1, MRP2, BSEP)
    Cryopreserved hepatocytes uptake
    Kinetic studies (Km, Vmax, intrinsic clearance)
  • Pharmacogenetics study
    OCT2A270S, OATP1B1*15, NTCP*2, MDR G2677T/A, BCRP Q141K

In vitro DDI study

  • Inhibition
    Screening of inhibitory potential of P450s, UGTs, Transporters
    Estimation of IC50 (Ki) value
  • Time-dependent inhibition
    IC50 shift assay, Estimation of KI and Kinact value
    GSH conjugate (reactive metabolite)
  • Induction
    Reporter assay (PXR)
    mRNA expression level in human hepatocytes (P450s, UGTs, Transporters)
    Protein expression level in tissue (P450s, UGTs, Transporters)
  • In vitro to in vivo prediction
    IVIVE prediction

Preclinical study

  • Linearity / Bioavailability
    IV/Oral administration PK
  • Mass balance
    Radio-labeled compound PK
  • Distribution
    Tissue distribution (brain, liver, kidney)
  • Metabolic profiling
    Metabolites profiling and Met ID
  • Biliary / Renal excretion
    Bile cannulation

Early Phase Clinical Development

  • Preclinical Prediction of Human PKs
    Microdosing study of hot compound and cold compound
    Allometry
    Physiologic Based Pharmacokinetics
  • Phase I study
    Pharmacologically guided dose escalation
    Human mass balance (cold/hot compound)
    Absolute bioavailability
    Drug-drug interaction potential study(cocktail study)
    Mechanism based drug-drug interaction study
    Genotype based ADME study
    Special population study(Renal/Hepatic dysfunction, Elderly, Gender)
    Bridging study
    Biologics
  • Pharmacokinetics/Pharmacodynamics
    Non-compartmental/Compartmental Analysis
    Population Pharmacokinetics/Pharmacodynamics
    Dose-Effect/Concentration Effect analysis
    Development of Biomarker