Antibody pharmacokinetics and pharmacodynamics
- PMID: 15389672
- DOI: 10.1002/jps.20178
Antibody pharmacokinetics and pharmacodynamics
Abstract
The U.S. Food and Drug administration (FDA) has approved several polyclonal antibody preparations and at least 18 monoclonal antibody preparations (antibodies, antibody fragments, antibody fusion proteins, etc.). These drugs, which may be considered as a diverse group of therapeutic proteins, are associated with several interesting pharmacokinetic characteristics. Saturable binding with target antigen may influence antibody disposition, potentially leading to nonlinear distribution and elimination. Independent of antigen interaction, concentration-dependent elimination may be expected for IgG antibodies, due to the influence of the Brambell receptor, FcRn, which protects IgG from catabolism. Antibody administration may induce the development of an endogenous antibody response, which may alter the pharmacokinetics of the therapeutic antibody. Additionally, the pharmacodynamics of antibodies are also complex; these drugs may be used for a wide array of therapeutic applications, and effects may be achieved by a variety of mechanisms. This article provides an overview of many of the complexities associated with antibody pharmacokinetics and pharmacodynamics.
Similar articles
-
Monoclonal antibody pharmacokinetics and pharmacodynamics.Clin Pharmacol Ther. 2008 Nov;84(5):548-58. doi: 10.1038/clpt.2008.170. Epub 2008 Sep 10. Clin Pharmacol Ther. 2008. PMID: 18784655
-
Are endosomal trafficking parameters better targets for improving mAb pharmacokinetics than FcRn binding affinity?Mol Immunol. 2013 Dec;56(4):660-74. doi: 10.1016/j.molimm.2013.05.008. Epub 2013 Aug 2. Mol Immunol. 2013. PMID: 23917469 Review.
-
Pharmacokinetics and biodistribution of genetically-engineered antibodies.Q J Nucl Med. 1998 Dec;42(4):225-41. Q J Nucl Med. 1998. PMID: 9973838 Review.
-
Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics.Proc Natl Acad Sci U S A. 2015 May 12;112(19):5997-6002. doi: 10.1073/pnas.1408766112. Epub 2015 Apr 27. Proc Natl Acad Sci U S A. 2015. PMID: 25918417 Free PMC article.
-
Effect of alpha-1-acid glycoprotein binding on pharmacokinetics and pharmacodynamics.Curr Drug Metab. 2013 Feb;14(2):226-38. Curr Drug Metab. 2013. PMID: 23092311 Review.
Cited by
-
Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus.J Drug Assess. 2013 Apr 12;2(1):40-8. doi: 10.3109/21556660.2013.792823. eCollection 2013. J Drug Assess. 2013. PMID: 27536436 Free PMC article.
-
Simulations of site-specific target-mediated pharmacokinetic models for guiding the development of bispecific antibodies.J Pharmacokinet Pharmacodyn. 2015 Feb;42(1):1-18. doi: 10.1007/s10928-014-9401-1. Epub 2015 Jan 6. J Pharmacokinet Pharmacodyn. 2015. PMID: 25559227
-
Endocytotic uptake of FITC-labeled anti-H. pylori egg yolk immunoglobulin Y in Candida yeast for detection of intracellular H. pylori.Front Microbiol. 2015 Feb 16;6:113. doi: 10.3389/fmicb.2015.00113. eCollection 2015. Front Microbiol. 2015. PMID: 25852651 Free PMC article.
-
An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer.Clin Pharmacokinet. 2013 Aug;52(8):657-72. doi: 10.1007/s40262-013-0060-y. Clin Pharmacokinet. 2013. PMID: 23553425
-
TRAIL-receptor 1 IgM antibodies strongly induce apoptosis in human cancer cells in vitro and in vivo.Oncoimmunology. 2016 May 4;5(5):e1131380. doi: 10.1080/2162402X.2015.1131380. eCollection 2016 May. Oncoimmunology. 2016. PMID: 27467950 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
