Monoclonal Antibody Pharmacokinetics and Pharmacodynamics
Top Cited Papers
- 10 September 2008
- journal article
- Published by Wiley in Clinical Pharmacology & Therapeutics
- Vol. 84 (5), 548-558
- https://doi.org/10.1038/clpt.2008.170
Abstract
More than 20 monoclonal antibodies have been approved as therapeutic drugs by the US Food and Drug Administration, and it is quite likely that the number of approved antibodies will double in the next 7-10 years. Antibody drugs show several desirable characteristics, including good solubility and stability, long persistence in the body, high selectivity and specificity, and low risk for bioconversion to toxic metabolites. However, many antibody drugs demonstrate attributes that complicate drug development, including very poor oral bioavailability, incomplete absorption following intramuscular or subcutaneous administration, nonlinear distribution, and nonlinear elimination. In addition, antibody administration often leads to an endogenous antibody response, which may alter the pharmacokinetics and efficacy of the therapeutic antibody. Antibodies have been developed for a wide range of disease conditions, with effects produced through a complex array of mechanisms. This article attempts to provide a brief overview of the main determinants of antibody pharmacokinetics and pharmacodynamics. Clinical Pharmacology & Therapeutics (2008); 84, 5, 548-558 doi:10.1038/clpt.2008.170.Keywords
This publication has 43 references indexed in Scilit:
- Integrated Cellular Bone Homeostasis Model for Denosumab Pharmacodynamics in Multiple Myeloma PatientsThe Journal of pharmacology and experimental therapeutics, 2008
- A mechanism‐based binding model for the population pharmacokinetics and pharmacodynamics of omalizumabBritish Journal of Clinical Pharmacology, 2007
- A Predictive Model of Therapeutic Monoclonal Antibody Dynamics and Regulation by the Neonatal Fc Receptor (FcRn)Annals of Biomedical Engineering, 2005
- Mechanisms of Intravenous Immunoglobulin Action in Immune Thrombocytopenic PurpuraHuman Immunology, 2005
- Pharmacokinetic Effects of 4C9, An Anti-FcRn Antibody, in Rats: Implications for the Use of FcRn Inhibitors for the Treatment of Humoral Autoimmune and Alloimmune ConditionsJournal of Pharmaceutical Sciences, 2005
- On the Prediction of the Human Response: A Recycled Mechanistic Pharmacokinetic/Pharmacodynamic ApproachBasic & Clinical Pharmacology & Toxicology, 2005
- Simultaneous Modeling of Abciximab Plasma Concentrations and ex Vivo Pharmacodynamics in Patients Undergoing Coronary AngioplastyThe Journal of pharmacology and experimental therapeutics, 2003
- Systemic Availability and Lymphatic Transport of Human Growth Hormone Administered by Subcutaneous InjectionJournal of Pharmaceutical Sciences, 2000
- Interspecies Scaling of Clearance and Volume of Distribution for Digoxin-Specific FabToxicology and Applied Pharmacology, 1996
- The OKT3 antibody response study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ tranplantationTransplant Immunology, 1995