Model-based drug development: the road to quantitative pharmacology

J Pharmacokinet Pharmacodyn. 2006 Jun;33(3):369-93. doi: 10.1007/s10928-006-9010-8. Epub 2006 Jun 13.


High development costs and low success rates in bringing new medicines to the market demand more efficient and effective approaches. Identified by the FDA as a valuable prognostic tool for fulfilling such a demand, model-based drug development is a mathematical and statistical approach that constructs, validates, and utilizes disease models, drug exposure-response models, and pharmacometric models to facilitate drug development. Quantitative pharmacology is a discipline that learns and confirms the key characteristics of new molecular entities in a quantitative manner, with goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans and enabling critical decision making. Model-based drug development serves as an integral part of quantitative pharmacology. This work reviews the general concept, basic elements, and evolving role of model-based drug development in quantitative pharmacology. Two case studies are presented to illustrate how the model-based drug development approach can facilitate knowledge management and decision making during drug development. The case studies also highlight the organizational learning that comes through implementation of quantitative pharmacology as a discipline. Finally, the prospects of quantitative pharmacology as an emerging discipline are discussed. Advances in this discipline will require continued collaboration between academia, industry and regulatory agencies.

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Clinical Trials as Topic / methods
  • Clinical Trials as Topic / statistics & numerical data
  • Computer Simulation*
  • Decision Making
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Industry / methods*
  • Drug Industry / statistics & numerical data
  • Drug Industry / trends
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Osteocalcin / blood
  • Osteoporosis, Postmenopausal / blood
  • Osteoporosis, Postmenopausal / drug therapy
  • Pharmacology / methods*
  • Pharmacology / statistics & numerical data
  • Pharmacology / trends
  • Raloxifene Hydrochloride / administration & dosage
  • Raloxifene Hydrochloride / pharmacokinetics
  • Selective Estrogen Receptor Modulators / administration & dosage
  • Selective Estrogen Receptor Modulators / pharmacokinetics
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Treatment Outcome


  • Antimetabolites, Antineoplastic
  • Biomarkers
  • Selective Estrogen Receptor Modulators
  • Deoxycytidine
  • Osteocalcin
  • Raloxifene Hydrochloride
  • Gemcitabine