Combination of cassette-dosing and microsampling for reduced animal usage for antibody pharmacokinetics in cynomolgus monkeys, wild-type mice, and human FcRn transgenic mice

Purpose The aim of this study was to develop a useful antibody PK evaluation tool using a combination of cassette-dosing and microsampling in mice and monkeys in order to reduce the number of animals used. Methods Cetuximab, denosumab, infliximab, and a mixture of the three antibodies, i.e., cassett...

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Bibliographic Details
Published in:Pharmaceutical research 2021-04, Vol.38 (4), p.583-592
Main Authors: Nagayasu, Miho, Ozeki, Kazuhisa
Format: Article
Language:English
Subjects:
Antibodies
Biochemistry
Biological products
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Denosumab
Dosage
Fc receptors
Genetic engineering
Infliximab
Jugular vein
Medical Law
Mice
Monoclonal antibodies
Neonates
Pharmacokinetics
Pharmacology/Toxicology
Pharmacy
Research Paper
Transgenic mice
Tumor necrosis factor-α
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Summary:Purpose The aim of this study was to develop a useful antibody PK evaluation tool using a combination of cassette-dosing and microsampling in mice and monkeys in order to reduce the number of animals used. Methods Cetuximab, denosumab, infliximab, and a mixture of the three antibodies, i.e., cassette-dosing, were administered intravenously to cynomolgus monkeys, C57BL/6J mice, and homozygous human neonatal Fc-receptor transgenic (Tg32) mice. Mouse blood was collected from one animal continuously via the jugular vein at nine points. Results In cynomolgus monkeys, infliximab showed faster elimination in the cassette-dosing group than in the single-dose group. Anti-drug antibody production was observed, but the PK parameters of the clearance and distribution volume were similar in both groups. In C57BL/6J and Tg32 mice, each of the plasma concentrations–time profiles after cassette-dosing were similar to those after single dosing. PK evaluation using a combination of cassette-dosing and microsampling in mice may reduce the number of mice used by approximately 90% compared with the conventional method. Conclusions The combination of antibody cassette-dosing and microsampling is a promising PK evaluation method as a high-throughput and reliable with reduced numbers of mice and cynomolgus monkeys.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-021-03028-6