Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins

Expert Opin Biol Ther. 2005 Sep:5 Suppl 1:S37-47. doi: 10.1517/14712598.5.1.s37.

Abstract

Although monoclonal antibodies (mAbs) constitute a major advance in therapeutics, their pharmacokinetic (PK) and pharmacodynamic (PD) properties are not fully understood. Saturable mechanisms are thought to occur in distribution and elimination of mAbs, which are protected from degradation by the Brambell's receptor (FcRn). The binding of mAbs to their target antigen explains part of their nonlinear PK and PD properties. The interindividual variability in mAb PK can be explained by several factors, including immune response against the biodrug and differences in the number of antigenic sites. The concentration-effect relationships of mAbs are complex and dependent on their mechanism of action. Interindividual differences in mAb PD can be explained by factors such as genetics and clinical status. PK and concentration-effect studies are necessary to design optimal dosing regimens. Because of their above-mentioned characteristics, the interindividual variability in their dose-response relationships must be studied by PK-PD modelling.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Binding Sites, Antibody
  • Biomarkers / metabolism
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • Clinical Trials as Topic
  • Crohn Disease / drug therapy
  • Crohn Disease / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Evaluation, Preclinical
  • Humans
  • Models, Biological
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Receptors, Fc / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacokinetics*
  • Recombinant Fusion Proteins / therapeutic use
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers
  • CD4 Antigens
  • FCGR3A protein, human
  • Receptors, Fc
  • Receptors, IgG
  • Recombinant Fusion Proteins
  • clenoliximab
  • Rituximab