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J Pharm Sci. 2015 May;104(5):1825-31. doi: 10.1002/jps.24368. Epub 2015 Jan 28.

Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

Author information

1
CVMD, Innovative Medicines, AstraZeneca R&D, Mölndal, S-431 83, Mölndal, Sweden.

Abstract

Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax ) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding.

KEYWORDS:

IgG antibody; clearance; diffusion; distribution; immunoassay; mathematical model; metabolic diseases; nontargeted FAb antibody; nontargeted full-length antibody; perfusion; pharmacokinetics

PMID:
25631774
DOI:
10.1002/jps.24368
[Indexed for MEDLINE]

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