Abstract
Increasing serum residence time of drugs by means of fusing them to albumin-binding domain antibodies (AlbudAbs™) has previously been documented. AlbudAbs™ provide a valuable method for increasing the efficacy of drugs by extending the time for which therapeutic levels of drug are present in the body and also for increasing the convenience to the patient by reducing the need for frequent dosing. Here, we describe methods that could be used preclinically to determine the suitability of drug-AlbudAbs™ for development. Particular focus is given to suggested in vivo study design which could enable the fitting of accurate PK parameters, assay methods for concentration determination of AlbudAbs™ in blood samples, and to the protocols used to fit PK parameters to AlbudAb™ concentration data. Whilst the examples cited here are focussed on the AlbudAb™ technology, similar methods could be used for assessing the success of other half-life extension technologies (drug Fc fusions, PEGylated drugs).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
St Onge EL, Miller SA (2010) Albiglutide; a new GLP-1 analogue for the treatment of type 2 diabetes. Expert Opin Biol Ther 10:801–806
Lee H (2003) Population pharmacokinetic and pharmacodynalic modelling of etanercept using logistic regression analysis. Clin Pharmacol Ther 73:348–365
Syed S et al (1997) Potent antithrombin activity and delayed clearance from the circulation characterise recombinant hirudin genetically fused to albumin. Blood 89:3243–3252
Osborn BL et al (2002) Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 303:540–548
Mohler KM et al (1993) Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151:1548–1561
Pasut G, Veronese FM (2009) PEGylation for improving the effectiveness of therapeutic biomolecules. Drugs Today 45:687–695
Holt LJ et al (2008) Anti-serum albumin domain antibodies for extending the half- lives of short lived drugs. Protein Eng Des Sel 21:283–288
Walker A et al (2010) Anti-serum albumin domain antibodies in the development of highly potent, efficacious and long-acting interferon. Protein Eng Des Sel 23:271–278
Peters T Jr (1985) Serum albumin. Adv Protein Chem 37:161–245
Ward ES et al (1989) Binding activities of a repertoire of single immunoglobulin variable domains secreted from Eschericia Coli. Nature 341:544–546
Rhyne PW et al (2009) Electrochemiluminescence in bioanalysis. Bioanalysis 1:919–935
Miao W (2008) Electrogenerated chemiluminescence and its biorelated applications. Chem Rev 108:2506–2553
DiStefano III (1982) Non-compartmental vs compartmental analysis: some bases for choice. Am J Physiol 243:R1–R6
Jacquez JA, Simon SP (1993) Qualitative theory of compartmental analysis. SIAM Rev 35:43–79
Acknowledgements
The authors were employees of Domantis Limited, and then subsequently of GlaxoSmithKline, at the time that this work was carried out.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Rycroft, D., Holt, L.J. (2012). Methods for Determining the PK Parameters of AlbudAbs™ and of Long Serum Half-Life Drugs Made Using the AlbudAb™ Technology. In: Saerens, D., Muyldermans, S. (eds) Single Domain Antibodies. Methods in Molecular Biology, vol 911. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-968-6_28
Download citation
DOI: https://doi.org/10.1007/978-1-61779-968-6_28
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-967-9
Online ISBN: 978-1-61779-968-6
eBook Packages: Springer Protocols