Combination of Cassette-dosing and Microsampling for Reduced Animal Usage for Antibody Pharmacokinetics in Cynomolgus Monkeys, Wild-type Mice, and Human FcRn Transgenic Mice

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2021 Mar 30

PMID 33782838

Citations 3

Authors

Miho Nagayasu

Kazuhisa Ozeki

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Igawa T, Ishii S, Tachibana T, Maeda A, Higuchi Y, Shimaoka S . Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization. Nat Biotechnol. 2010; 28(11):1203-7. DOI: 10.1038/nbt.1691. View

Kinder M, Greenplate A, Strohl W, Jordan R, Brezski R . An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions. MAbs. 2015; 7(3):494-504. PMC: 4622058. DOI: 10.1080/19420862.2015.1022692. View

Sampei Z, Haraya K, Tachibana T, Fukuzawa T, Shida-Kawazoe M, Gan S . Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody. PLoS One. 2018; 13(12):e0209509. PMC: 6310256. DOI: 10.1371/journal.pone.0209509. View

Mackness B, Jaworski J, Boudanova E, Park A, Valente D, Mauriac C . Antibody Fc engineering for enhanced neonatal Fc receptor binding and prolonged circulation half-life. MAbs. 2019; 11(7):1276-1288. PMC: 6748615. DOI: 10.1080/19420862.2019.1633883. View

Joyce A, Wang M, Lawrence-Henderson R, Filliettaz C, Leung S, Xu X . One mouse, one pharmacokinetic profile: quantitative whole blood serial sampling for biotherapeutics. Pharm Res. 2014; 31(7):1823-33. DOI: 10.1007/s11095-013-1286-y. View

Nakamura G, Ozeki K, Nagayasu M, Nambu T, Nemoto T, Hosoya K . Predicting Method for the Human Plasma Concentration-Time Profile of a Monoclonal Antibody from the Half-life of Non-human Primates. Biol Pharm Bull. 2020; 43(5):823-830. DOI: 10.1248/bpb.b19-01042. View

Haraya K, Tachibana T, Nanami M, Ishigai M . Application of human FcRn transgenic mice as a pharmacokinetic screening tool of monoclonal antibody. Xenobiotica. 2014; 44(12):1127-34. DOI: 10.3109/00498254.2014.941963. View

Oitate M, Nakayama S, Ito T, Kurihara A, Okudaira N, Izumi T . Prediction of human plasma concentration-time profiles of monoclonal antibodies from monkey data by a species-invariant time method. Drug Metab Pharmacokinet. 2011; 27(3):354-9. DOI: 10.2133/dmpk.dmpk-11-sh-059. View

Oitate M, Masubuchi N, Ito T, Yabe Y, Karibe T, Aoki T . Prediction of human pharmacokinetics of therapeutic monoclonal antibodies from simple allometry of monkey data. Drug Metab Pharmacokinet. 2011; 26(4):423-30. DOI: 10.2133/dmpk.dmpk-11-rg-011. View

10.

Avery L, Wang M, Kavosi M, Joyce A, Kurz J, Fan Y . Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. MAbs. 2016; 8(6):1064-78. PMC: 4968115. DOI: 10.1080/19420862.2016.1193660. View

11.

Dostalek M, Prueksaritanont T, Kelley R . Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates. MAbs. 2017; 9(5):756-766. PMC: 5524161. DOI: 10.1080/19420862.2017.1323160. View

12.

Conner K, Pastuskovas C, Soto M, Thomas V, Wagner M, Rock D . Preclinical characterization of the ADME properties of a surrogate anti-IL-36R monoclonal antibody antagonist in mouse serum and tissues. MAbs. 2020; 12(1):1746520. PMC: 7188401. DOI: 10.1080/19420862.2020.1746520. View

13.

Jiang H, Zeng J, Titsch C, Voronin K, Akinsanya B, Luo L . Fully validated LC-MS/MS assay for the simultaneous quantitation of coadministered therapeutic antibodies in cynomolgus monkey serum. Anal Chem. 2013; 85(20):9859-67. DOI: 10.1021/ac402420v. View

14.

Li H, Ortiz R, Tran L, Salimi-Moosavi H, Malella J, James C . Simultaneous analysis of multiple monoclonal antibody biotherapeutics by LC-MS/MS method in rat plasma following cassette-dosing. AAPS J. 2012; 15(2):337-46. PMC: 3675729. DOI: 10.1208/s12248-012-9435-5. View

15.

Liu B, Chang J, Gordon W, Isbell J, Zhou Y, Tuntland T . Snapshot PK: a rapid rodent in vivo preclinical screening approach. Drug Discov Today. 2008; 13(7-8):360-7. DOI: 10.1016/j.drudis.2007.10.014. View

16.

Manitpisitkul P, White R . Whatever happened to cassette-dosing pharmacokinetics?. Drug Discov Today. 2004; 9(15):652-8. DOI: 10.1016/S1359-6446(04)03137-X. View

17.

Nagilla R, Nord M, McAtee J, Jolivette L . Cassette dosing for pharmacokinetic screening in drug discovery: comparison of clearance, volume of distribution, half-life, mean residence time, and oral bioavailability obtained by cassette and discrete dosing in rats. J Pharm Sci. 2011; 100(9):3862-74. DOI: 10.1002/jps.22525. View

18.

Smith N, Raynaud F, Workman P . The application of cassette dosing for pharmacokinetic screening in small-molecule cancer drug discovery. Mol Cancer Ther. 2007; 6(2):428-40. DOI: 10.1158/1535-7163.MCT-06-0324. View

19.

Musteata F . Pharmacokinetic applications of microdevices and microsampling techniques. Bioanalysis. 2010; 1(1):171-85. DOI: 10.4155/bio.09.18. View

20.

Rahavendran S, Vekich S, Skor H, Batugo M, Nguyen L, Shetty B . Discovery pharmacokinetic studies in mice using serial microsampling, dried blood spots and microbore LC-MS/MS. Bioanalysis. 2012; 4(9):1077-95. DOI: 10.4155/bio.12.85. View