Physiologically based pharmacokinetic model for T84.66: A monoclonal anti-CEA antibody
dc.contributor.author | Urva, Shweta R. | en_US |
dc.contributor.author | Yang, Victor C. | en_US |
dc.contributor.author | Balthasar, Joseph P. | en_US |
dc.date.accessioned | 2010-02-02T15:31:29Z | |
dc.date.available | 2011-03-01T16:26:44Z | en_US |
dc.date.issued | 2010-03 | en_US |
dc.identifier.citation | Urva, Shweta R.; Yang, Victor C.; Balthasar, Joseph P. (2010). "Physiologically based pharmacokinetic model for T84.66: A monoclonal anti-CEA antibody." Journal of Pharmaceutical Sciences 99(3): 1582-1600. <http://hdl.handle.net/2027.42/64917> | en_US |
dc.identifier.issn | 0022-3549 | en_US |
dc.identifier.issn | 1520-6017 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/64917 | |
dc.description.abstract | Antibodies directed against tumor associated antigens are being increasingly used for detection and treatment of cancers; however, there is an incomplete understanding of the physiological determinants of antibody pharmacokinetics and tumor distribution. The purpose of this study is to (a) compare the plasma pharmacokinetics of T84.66, a monoclonal anti-CEA antibody directed against tumor associated carcinoembryonic antigen (CEA), in control and CEA expressing LS174T xenograft bearing mice, and (b) to develop a physiologically based pharmacokinetic (PBPK) model capable of integrating the influence of CEA and the IgG salvage receptor, FcRn, on T84.66 disposition. T84.66 pharmacokinetics were studied following i.v. administration (1, 10, 25 mg/kg) in control and xenograft bearing mice. In control mice, no significant differences in clearance were observed across the dose range studied. In mice bearing xenograft tumors, clearance was increased by four- to sevenfold, suggesting the presence of a “target mediated” elimination pathway. T84.66 plasma disposition was characterized with a PBPK model, and the model was applied to successfully predict antibody concentrations in tumor tissue. The PBPK model will be used to assist in the development of antibody-based targeting strategies for CEA-positive tumors. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1582–1600, 2010 | en_US |
dc.format.extent | 333822 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry | en_US |
dc.title | Physiologically based pharmacokinetic model for T84.66: A monoclonal anti-CEA antibody | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmaceutical Sciences, College of Pharmacy, The University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109-1065 | en_US |
dc.contributor.affiliationother | Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14260 | en_US |
dc.contributor.affiliationother | Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14260 ; Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14260. Telephone: 716-645-2842 ext 270; Fax: 716-645-3693. | en_US |
dc.identifier.pmid | 19774657 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/64917/1/21918_ftp.pdf | |
dc.identifier.doi | 10.1002/jps.21918 | en_US |
dc.identifier.source | Journal of Pharmaceutical Sciences | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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