Mechanism-based pharmacokinetic-pharmacodynamic modeling - A new classification of biomarkers

被引:113
|
作者
Danhof, M
Alvan, G
Dahl, SG
Kuhlmann, J
Paintaud, G
机构
[1] Leiden Univ, Div Pharmacol, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands
[2] Med Prod Agcy, S-75125 Uppsala, Sweden
[3] Univ Tromso, Fac Med, Dept Pharmacol, N-9037 Tromso, Norway
[4] Bayer HealthCare AG, Pharma Res Ctr, Business Grp Pharma, Inst Clin Pharmacol, D-42096 Wuppertal, Germany
[5] Univ Tours, Fac Med, Pharmacol Lab, F-37032 Tours, France
关键词
genotype; molecular target activation; molecular target occupancy; pathophysiological measures; physiological measures;
D O I
10.1007/s11095-005-5882-3
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
In recent years, pharmacokinetic/pharmacodynamic (PK/PD) modeling has developed from an empirical descriptive discipline into a mechanistic science that can be applied at all stages of drug development. Mechanism-based PK/PD models differ from empirical descriptive models in that they contain specific expressions to characterize processes on the causal path between drug administration and effect. Mechanism-based PK/PD models have much improved properties for extrapolation and prediction. As such, they constitute a scientific basis for rational drug discovery and development. In this report, a novel classification of biomarkers is proposed. Within the context of mechanism-based PK/PD modeling, a biomarker is defined as a measure that characterizes, in a strictly quantitative manner, a process, which is on the causal path between drug administration and effect. The new classification system distinguishes seven types of biomarkers: type 0, genotype/phenotype determining drug response; type 1, concentration of drug or drug metabolite; type 2, molecular target occupancy; type 3, molecular target activation; type 4, physiological measures; type 5, pathophysiological measures; and type 6, clinical ratings. In this paper, the use of the new biomarker classification is discussed in the context of the application of mechanism-based PK/PD analysis in drug discovery and development.
引用
收藏
页码:1432 / 1437
页数:6
相关论文
共 50 条
  • [21] Biomarkers, Validation and Pharmacokinetic-Pharmacodynamic Modelling
    Wayne A. Colburn
    Jean W. Lee
    Clinical Pharmacokinetics, 2003, 42 : 997 - 1022
  • [22] The role of mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modelling in translational research of biologics
    Agoram, Balaji M.
    Martin, Steven W.
    van der Graaf, Piet H.
    DRUG DISCOVERY TODAY, 2007, 12 (23-24) : 1018 - 1024
  • [23] Mechanism-based pharmacokinetic-pharmacodynamic models of in vitro fungistatic and fungicidal effects against Candida albicans
    Venisse, Nicolas
    Gregoire, Nicolas
    Marliat, Manuella
    Couet, William
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (03) : 937 - 943
  • [24] CONCEPTS AND USEFULNESS OF PHARMACOKINETIC-PHARMACODYNAMIC MODELING
    HOLFORD, NHG
    FUNDAMENTAL & CLINICAL PHARMACOLOGY, 1990, 4 : S93 - S101
  • [25] APPLICATION OF PHARMACOKINETIC-PHARMACODYNAMIC MODELING TO ANALGESIA
    INTURRISI, CE
    COLBURN, WA
    ADVANCES IN PAIN RESEARCH AND THERAPY, 1986, 8 : 441 - 452
  • [26] Biomarkers and pharmacokinetic-pharmacodynamic studies of immunosuppressive agents
    Paintaud, G
    Bénéton, M
    Watier, H
    THERAPIE, 2004, 59 (02): : 179 - 183
  • [27] Pharmacokinetic-Pharmacodynamic Modeling of Propofol in Children
    Rigouzzo, Agnes
    Servin, Frederique
    Constant, Isabelle
    ANESTHESIOLOGY, 2010, 113 (02) : 343 - 352
  • [28] PHARMACOKINETIC-PHARMACODYNAMIC AND METABOLITE MODELING WITH TOPFIT
    TANSWELL, P
    HEINZEL, G
    WEISENBERGER, H
    ROTH, W
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, 1995, 33 (10) : 550 - 554
  • [29] Pharmacokinetic-pharmacodynamic modeling of mivacurium in rats
    Troconiz, IF
    Garrido, MJ
    Garcia, E
    Suarez, E
    Calvo, R
    JOURNAL OF PHARMACEUTICAL SCIENCES, 1997, 86 (02) : 252 - 256
  • [30] Structural modeling: Simultaneous pharmacokinetic-pharmacodynamic modeling
    Gambus, PL
    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY, 1996, 18 : 47 - 48