Anatomical, Physiological, and Experimental Factors Affecting the Bioavailability of sc-Administered Large Biotherapeutics

Subcutaneous route of administration is highly desirable for protein therapeutics. It improves patient compliance and quality of life (McDonald TA, Zepeda ML, Tomlinson MJ, Bee WH, Ivens IA. 2010. Curr Opin Mol Ther 12(4):461–470; Dychter SS, Gold DA, Haller MF. 2012. J Infus Nurs 35(3):154–160), wh...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical sciences 2015-02, Vol.104 (2), p.301-306
Main Authors: Fathallah, Anas M., Balu-Iyer, Sathy V.
Format: Article
Language:English
Subjects:
absorption
bioavailability
Biological Availability
Biological Products - administration & dosage
Biological Products - metabolism
Biological Products - pharmacokinetics
Biological Therapy
biotechnology
Humans
Injections, Subcutaneous
preclinical pharmacokinetics
proteins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Subcutaneous route of administration is highly desirable for protein therapeutics. It improves patient compliance and quality of life (McDonald TA, Zepeda ML, Tomlinson MJ, Bee WH, Ivens IA. 2010. Curr Opin Mol Ther 12(4):461–470; Dychter SS, Gold DA, Haller MF. 2012. J Infus Nurs 35(3):154–160), while reducing healthcare cost (Dychter SS, Gold DA, Haller MF. 2012. J Infus Nurs 35(3):154–160). Recent evidence also suggests that sc administration of protein therapeutics can increase tolerability to some treatments such as intravenous immunoglobulin therapy by administering it subcutaneously (subcutaneous immunoglobulin therapy SCIG), which will reduce fluctuation in plasma drug concentration (Kobrynski L. 2012. Biologics 6:277–287). Furthermore, sc administration may reduce the risk of systemic infections associated with i.v. infusion (McDonald TA, Zepeda ML, Tomlinson MJ, Bee WH, Ivens IA. 2010. Curr Opin Mol Ther 12(4):461–470; Dychter SS, Gold DA, Haller MF. 2012. J Infus Nurs 35(3):154–160). This route, however, has its challenges, especially for large multidomain proteins. Poor bioavailability and poor scalability from preclinical models are often cited. This commentary will discuss barriers to sc absorption as well as physiological and experimental factors that could affect pharmacokinetics of subcutaneously administered large protein therapeutics in preclinical models. A mechanistic pharmacokinetic model is proposed as a potential tool to address the issue of scalability of sc pharmacokinetic from preclinical models to humans.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.24277