Subcutaneous Absorption of Biotherapeutics: Knowns and Unknowns

Richter, Wolfgang F.; Jacobsen, Björn

doi:10.1124/dmd.114.059238

Cited by 235Monoclonal and Polyclonal Antibodies ResearchBiosimilars and Bioanalytical MethodsIntramuscular injections and effects

Subcutaneous Absorption of Biotherapeutics: Knowns and Unknowns

Richter, Wolfgang F., Jacobsen, Björn·2014·Drug Metabolism and Disposition

DOI 10.1124/dmd.114.059238

Open this paper in CoChat — free account

Abstract

Subcutaneous administration of biotherapeutics offers several potential advantages compared with intravenous administration. Many biotherapeutics, both marketed or in development, are administered via the subcutaneous route. This minireview provides an overview of the presystemic absorption processes following subcutaneous administration, the resulting pharmacokinetics after subcutaneous administration, and provides recent case examples of the development of subcutaneous administered drugs with a focus on monoclonal antibodies. Subcutaneous absorption of biotherapeutics is relatively slow and mostly incomplete. Knowledge of the subcutaneous tissue is important to understand the absorption kinetics after subcutaneous administration. Transport in the subcutis to the absorbing blood or lymph capillaries appears to be a major contributor to the slow subcutaneous absorption. Larger proteins (>20 kDa) are mostly absorbed via the lymphatic system, although potential species differences are not fully understood yet. Also, the presystemic catabolism leading to incomplete bioavailability is little understood, both the involved enzymes and its translation across species. For IgGs, binding to the neonatal Fc receptor is important to obtain a high bioavailability. Overall, several aspects of subcutaneous absorption are still poorly understood, which hampers, e.g., translation across species. Further research in this area is warranted.

Integrity signals

Registry

Crossref · 10.1124/dmd.114.059238

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Understanding of the impact of various anatomic injection sites on subcutaneous absorption remains limited.
“As understanding of the impact of the various anatomic injection sites on subcutaneous absorption remains limited [10]”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [10]
Following subcutaneous injection, biotherapeutics with molecular weights of > 20 kDa exhibit limited transport into blood capillaries and cross into the systemic circulation predominantly via the lymphatics.
“Unlike small molecules, biotherapeutics with molecular weights of > 20 kDa exhibit limited transport into the blood capillaries and cross into the circulation system predominantly via the lymphatics [10, 71].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [10]

Monoclonal Antibody Pharmacokinetics and Pharmacodynamics
Wang, W., Wang, E., & Balthasar, J. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.170 · Cited by 978 · see citing works
Interstitial-lymphatic mechanisms in the control of extracellular fluid volume
Aukland, K., & Reed, R. K. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.1.1 · Cited by 938 · see citing works
The physiology of the lymphatic system
Swartz, M. A. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00150-8 · Cited by 738 · see citing works
Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer
Wiig, H., & Swartz, M. A. (2012) · Physiological Reviews · doi:10.1152/physrev.00037.2011 · Cited by 726 · see citing works
Patterns of lymphatic drainage in the adult laboratory rat.
Tilney, N. L. (1971) · PubMed · Cited by 404 · see citing works
Diffusion and convection in normal and neoplastic tissues.
Swabb, E. A., Wei, J., & Gullino, P. M. (1974) · PubMed · Cited by 398 · see citing works
Effect of Molecular Weight on the Lymphatic Absorption of Water-Soluble Compounds Following Subcutaneous Administration
Supersaxo, A., Hein, W. R., & Steffen, H. (1990) · Pharmaceutical Research · doi:10.1023/a:1015880819328 · Cited by 386 · see citing works
Mechanistic Determinants of Biotherapeutics Absorption Following SC Administration
Richter, W. F., Bhansali, S. G., & Morris, M. E. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9367-0 · Cited by 377 · see citing works
Self-citation
Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration
Frost, G. I. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.4.4.427 · Cited by 323 · see citing works
A recombinant human enzyme for enhanced interstitial transport of therapeutics
Bookbinder, L. H., Hofer, A., Haller, M. F., Zepeda, M. L., Keller, G.-A., Lim, J. E., Edgington, T. S., Shepard, H. M., Patton, J. S., & Frost, G. I. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.05.027 · Cited by 282 · see citing works
Structure, Function, and Molecular Control of the Skin Lymphatic System
Skobe, M., & Detmar, M. J. (2000) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1087-0024.2000.00001.x · Cited by 260 · see citing works
Subcutaneous drug delivery and the role of the lymphatics
McLennan, D. N., Porter, C. J. H., & Charman, S. A. (2005) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2005.05.006 · Cited by 259 · see citing works
Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration
Hale, G., Rebello, P., Brettman, L. R., Fegan, C., Kennedy, B., Kimby, E. K., Leach, M., Lundin, J., Mellstedt, H., Moreton, P., et al. (2004) · Blood · doi:10.1182/blood-2004-02-0593 · Cited by 181 · see citing works
Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy
Modi, S., Stanton, A. W. B., Svensson, W. E., Peters, A. M., Mortimer, P. S., & Levick, J. R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.130401 · Cited by 167 · see citing works
Improving the outcomes of biopharmaceutical delivery via the subcutaneous route by understanding the chemical, physical and physiological properties of the subcutaneous injection site
Kinnunen, H. M., & Mrsny, R. J. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.011 · Cited by 164 · see citing works
Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration
Zheng, Y., Tesar, D. B., Benincosa, L., Birnböck, H., Boswell, C. A., Bumbaca, D., Cowan, K. J., Danilenko, D. M., Daugherty, A. L., Fielder, P. J., et al. (2012) · mAbs · doi:10.4161/mabs.4.2.19387 · Cited by 149 · see citing works
Self-citation
A sensitive in vivo model for quantifying interstitial convective transport of injected macromolecules and nanoparticles
Reddy, S. T., Berk, D. A., Jain, R. K., & Swartz, M. A. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00389.2006 · Cited by 145 · see citing works
Subcutaneous administration of biotherapeutics: current experience in animal models.
McDonald, T. A., Zepeda, M. L., Tomlinson, M. J., Bee, W. H., & Ivens, I. A. (2010) · PubMed · Cited by 135 · see citing works
The Antibody Drug Absorption Following Subcutaneous or Intramuscular Administration and Its Mathematical Description by Coupling Physiologically Based Absorption Process with the Conventional Compartment Pharmacokinetic Model
Zhao, L. Y., Ji, P., Li, Z., Roy, P., & Sahajwalla, C. G. (2013) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.4 · Cited by 127 · see citing works
Structure and Function of Lymphatics
Ryan, T. J. (1989) · Journal of Investigative Dermatology · doi:10.1038/jid.1989.4 · Cited by 127 · see citing works
LYMPHATIC FLOW IN HUMAN SUBJECTS AS INDICATED BY THE DISAPPEARANCE OF I131-LABELED ALBUMIN FROM THE SUBCUTANEOUS TISSUE*†
Hollander, W., Reilly, P. J., & Burrows, B. A. (1961) · Journal of Clinical Investigation · doi:10.1172/jci104248 · Cited by 108 · see citing works
Subcutaneous Absorption of Monoclonal Antibodies: Role of Dose, Site of Injection, and Injection Volume on Rituximab Pharmacokinetics in Rats
Kagan, L., Turner, M. R., Balu‐Iyer, S. V., & Mager, D. E. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0578-3 · Cited by 105 · see citing works
Absorption kinetics of subcutaneously injected insulin
Berger, M., Halban, P. A., Girardier, L., Seydoux, J., Offord, R. E., & Renold, A. E. (1979) · Diabetologia · doi:10.1007/bf01222209 · Cited by 100 · see citing works
Subcutaneous Bioavailability of Golimumab at 3 Different Injection Sites in Healthy Subjects
Xu, Z., Wang, Q., Zhuang, Y., Frederick, B., Yan, H., Bouman‐Thio, E., Marini, J. C., Keen, M., Snead, D., Davis, H. M., et al. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009340782 · Cited by 97 · see citing works
The role of the lymphatic system in subcutaneous absorption of macromolecules in the rat model
Kagan, L., Gershkovich, P., Mendelman, A., Amsili, S., Ezov, N., & Hoffman, A. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2007.04.002 · Cited by 93 · see citing works
Transport in lymphatic capillaries. II. Microscopic velocity measurement with fluorescence photobleaching
Berk, D. A., Swartz, M. A., Leu, A. J., & Jain, R. K. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.270.1.h330 · Cited by 87 · see citing works
Lymphatic Transport and Catabolism of Therapeutic Proteins after Subcutaneous Administration to Rats and Dogs
Wang, W., Chen, N., Shen, X., Cunningham, P. K., Fauty, S. E., Michel, K. B., Wang, B., Hong, X., Adreani, C. M., Nunes, C. N., et al. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.043604 · Cited by 86 · see citing works
Subcutaneous bioavailability of therapeutic antibodies as a function of FcRn binding affinity in mice
Deng, R., Meng, Y. G., Hoyte, K., Lutman, J., Lu, Y., Iyer, S., DeForge, L. E., Theil, F., Fielder, P. J., & Prabhu, S. (2012) · mAbs · doi:10.4161/mabs.4.1.18543 · Cited by 83 · see citing works
Pain Assessment of Subcutaneous Injections
Jørgensen, J. T., Rømsing, J., Rasmussen, M., Sonnergaard, J. M., Vang, L. P., & Musaeus, L. (1996) · Annals of Pharmacotherapy · doi:10.1177/106002809603000703 · Cited by 83 · see citing works
Systemic Availability and Lymphatic Transport of Human Growth Hormone Administered by Subcutaneous Injection
Charman, S. A., Segrave, A. M., Edwards, G. A., & Porter, C. J. H. (2000) · Journal of Pharmaceutical Sciences · doi:10.1002/(sici)1520-6017(200002)89:2 · Cited by 83 · see citing works
Interspecies Comparisons of Pharmacokinetics and Pharmacodynamics of Recombinant Human Erythropoietin
Woo, S., & Jusko, W. J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015248 · Cited by 72 · see citing works
Effects of the Anatomical Region Used for Insulin Injections on Glycemia in Type I Diabetes Subjects
Bantle, J. P., Neal, L., & Frankamp, L. M. (1993) · Diabetes Care · doi:10.2337/diacare.16.12.1592 · Cited by 70 · see citing works
Receptor-Mediated Pharmacokinetic/Pharmacodynamic Model of Interferon-β 1a in Humans
Mager, D. E., & Jusko, W. J. (2002) · Pharmaceutical Research · doi:10.1023/a:1020468902694 · Cited by 63 · see citing works
Fluorescence Imaging of the Lymph Node Uptake of Proteins in Mice after Subcutaneous Injection: Molecular Weight Dependence
Wu, F. P., Bhansali, S. G., Law, W., Bergey, E. J., Prasad, P. N., & Morris, M. E. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0708-6 · Cited by 63 · see citing works
Structure and Function of Lymphatics.
Ryan, T. J. (1989) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12580899 · Cited by 61 · see citing works
Electrostatic Interactions of Monoclonal Antibodies With Subcutaneous Tissue
Mach, H., Gregory, S., Mackiewicz, A. L., Mittal, S., Lalloo, A., Kirchmeier, M. J., & Shameem, M. (2011) · Therapeutic Delivery · doi:10.4155/tde.11.31 · Cited by 60 · see citing works
Development of a Subcutaneous Formulation for Trastuzumab - Nonclinical and Clinical Bridging Approach to the Approved Intravenous Dosing Regimen
Bittner, B., Richter, W., Hourcade‐Potelleret, F., McIntyre, C., Herting, F., Zepeda, M. L., & Schmidt, J. (2012) · Arzneimittelforschung · doi:10.1055/s-0032-1321831 · Cited by 57 · see citing works
Self-citation
The Lymphatic System Plays a Major Role in the Intravenous and Subcutaneous Pharmacokinetics of Trastuzumab in Rats
Dahlberg, A. H., Kaminskas, L. M., Smith, A., Nicolazzo, J. A., Porter, C. J. H., Bulitta, J. B., & McIntosh, M. P. (2013) · Molecular Pharmaceutics · doi:10.1021/mp400464s · Cited by 56 · see citing works
Influence of improved FcRn binding on the subcutaneous bioavailability of monoclonal antibodies in cynomolgus monkeys
Datta-Mannan, A., Witcher, D. R., Lu, J., & Wroblewski, V. J. (2012) · mAbs · doi:10.4161/mabs.4.2.19364 · Cited by 53 · see citing works
The pharmacokinetics of recombinant human erythropoietin after subcutaneous injection at different sites
Jensen, J. D., Jensen, L. W., & Madsen, J. K. (1994) · European Journal of Clinical Pharmacology · doi:10.1007/bf00194401 · Cited by 49 · see citing works
Review of the Mechanism of Action and Clinical Efficacy of Recombinant Human Hyaluronidase Coadministration with Current Prandial Insulin Formulations
Muchmore, D. B., & Vaughn, D. E. (2010) · Journal of Diabetes Science and Technology · doi:10.1177/193229681000400223 · Cited by 49 · see citing works
Mechanisms of Subcutaneous Absorption of Rituximab in Rats
Kagan, L., & Mager, D. E. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.048496 · Cited by 49 · see citing works
Subcutaneous injection technique
Hunter, J. (2008) · Nursing Standard · doi:10.7748/ns2008.01.22.21.41.c6418 · Cited by 45 · see citing works
In Vivo Fluorescence Imaging of IgG1 Aggregates After Subcutaneous and Intravenous Injection in Mice
Filipe, V., Que, I., Carpenter, J. F., Löwik, C., & Jiskoot, W. (2014) · Pharmaceutical Research · doi:10.1007/s11095-013-1154-9 · Cited by 39 · see citing works
Plasma and Lymph Pharmacokinetics of Recombinant Human Interleukin-2 and Polyethylene Glycol-Modified Interleukin-2 in Pigs
Chen, S. A., Sawchuk, R. J., Brundage, R. C., Horvath, C. J., Mendenhall, H. V., Gunther, R. A., & Braeckman, R. A. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39226-2 · Cited by 38 · see citing works
Development of a Subcutaneous Formulation for Trastuzumab – Nonclinical and Clinical Bridging Approach to the Approved Intravenous Dosing Regimen
Bittner, B., Richter, W., Hourcade‐Potelleret, F., McIntyre, C., Herting, F., Zepeda, M. L., & Schmidt, J. (2013) · Drug Research · doi:10.1055/s-0033-1357211 · Cited by 38 · see citing works
Self-citation
Non-Clinical Pharmacokinetic/Pharmacodynamic and Early Clinical Studies Supporting Development of a Novel Subcutaneous Formulation for the Monoclonal Antibody Rituximab
Bittner, B., Richter, W., Hourcade-Potelleret, F., Herting, F., & Schmidt, J. (2014) · Drug Research · doi:10.1055/s-0033-1363993 · Cited by 32 · see citing works
Self-citation
Enhanced Bioavailability of Subcutaneously Injected Insulin by Pretreatment with Ointment Containing Protease Inhibitors
Takeyama, M., Ishida, T., Kokubu, N., Komada, F., Iwakawa, S., Okumura, K., & Hori, R. (1991) · Pharmaceutical Research · doi:10.1023/a:1015878222769 · Cited by 31 · see citing works
Monitoring pulse rate
Rawlings‐Anderson, K., & Hunter, J. (2008) · Nursing Standard · doi:10.7748/ns.22.31.41.s41 · Cited by 23 · see citing works
Pharmacokinetics and metabolic effects of growth hormone injected subcutaneously in growth hormone deficient patients: thigh versus abdomen
Laursen, T., Jørgensen, J. O. L., & Christiansen, J. S. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb03934.x · Cited by 22 · see citing works
Fate of porcine and human insulin at the subcutaneous injection site. II. In vitro degradation of insulins in the subcutaneous tissue of the rat.
Komada, F., Okumura, K., & Hori, R. (1985) · Journal of Pharmacobio-Dynamics · doi:10.1248/bpb1978.8.33 · Cited by 21 · see citing works
Lymphatic transport of recombinant human tumor necrosis factor in rats.
KOJIMA, K., TAKAHASHI, T., & NAKANISHI, Y. (1988) · Journal of Pharmacobio-Dynamics · doi:10.1248/bpb1978.11.700 · Cited by 20 · see citing works
First-line treatment of chronic lymphocytic leukemia: role of alemtuzumab
Schweighofer, C. D. (2010) · OncoTargets and Therapy · doi:10.2147/ott.s3099 · Cited by 20 · see citing works
Lymphatic Absorption, Metabolism, and Excretion of a Therapeutic Peptide in Dogs and Rats
Zou, Y., Bateman, T. J., Adreani, C. M., Shen, X., Cunningham, P. K., Wang, B., Trinh, T., Christine, A., Hong, X., da Silva, C. N., et al. (2013) · Drug Metabolism and Disposition · doi:10.1124/dmd.113.051524 · Cited by 20 · see citing works
An appraisal of subcutaneous trastuzumab: a new formulation meeting clinical needs
Launay‐Vacher, V. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2289-4 · Cited by 17 · see citing works
Interstitial exclusion of albumin in rabbit lung during development of pulmonary oedema
Negrini, D., Tenstad, O., & Wiig, H. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.00907.x · Cited by 11 · see citing works
Subcutaneous bioavailability of a PRIMATIZEDTMIgG1 Anti-Human CD4 monoclonal antibody is dose dependent in transgenic mice bearing human CD4
Davis, C. B., & Bugelski, P. J. (1998) · Drug Delivery · doi:10.3109/10717549809031384 · Cited by 10 · see citing works
Capillary dynamics and the interstitial fluid-lymphatic system
Waterhouse, J. M., Sawdon, M. A., & Kirkman, E. (2007) · Anaesthesia & intensive care medicine · doi:10.1016/j.mpaic.2006.12.012 · Cited by 9 · see citing works
Interstitial exclusion of albumin in rabbit lung during development of pulmonary oedema
Negrini, D., Tenstad, O., & Wiig, H. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.038182 · Cited by 9 · see citing works
Demonstration of Initial Lymphatics in Excised Human Skin Using an Extension Technique and Dye Injection
Lubach, D., Nissen, S., & Neukam, D. (1991) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12471131 · Cited by 8 · see citing works
Care and management of patients with skin-tunnelled catheters
Green, J. (2008) · Nursing Standard · doi:10.7748/ns2008.06.22.42.41.c6580 · Cited by 6 · see citing works
Dramatic Improvement of Subcutaneous Insulin Resistance with Nafamostat Ointment Treatment
Kawashima, S., Kaneto, H., Sakamoto, K., 本庄郁子, Yasuda, T., Kuroda, A., Shiraiwa, T., Kasami, R., Matsuoka, T., Yamasaki, Y., et al. (2008) · Diabetes Care · doi:10.2337/dc07-2161 · Cited by 5 · see citing works
Capillary dynamics and the interstitial fluid-lymphatic system
Waterhouse, J. M., Sawdon, M. A., & Kirkman, E. (2010) · Anaesthesia & intensive care medicine · doi:10.1016/j.mpaic.2009.10.017 · Cited by 4 · see citing works

Flagged first, then by citations

Sorted by citations

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities
Bittner, B., Richter, W., & Schmidt, J. (2018) · BioDrugs · doi:10.1007/s40259-018-0295-0 · Cited by 447 · see citing works
Self-citation
Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins
Liming, L. (2017) · Protein & Cell · doi:10.1007/s13238-017-0408-4 · Cited by 394 · see citing works
Considerations for the Design of Antibody-Based Therapeutics
Goulet, D. R., & Atkins, W. M. (2019) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2019.05.031 · Cited by 305 · see citing works
A review of Formulations of Commercially Available Antibodies
Strickley, R. G., & Lambert, W. J. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.03.017 · Cited by 273 · see citing works
Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease
Schreiber, S., Ben‐Horin, S., Leszczyszyn, J., Dudkowiak, R., Lahat, A., Gawdis-Wojnarska, B., Puķītis, A., Horynski, M., Farkas, K., Kierkuś, J., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.02.068 · Cited by 240 · see citing works
Subcutaneous delivery of monoclonal antibodies: How do we get there?
Viola, M., Sequeira, J. A. D., Seiça, R. M. F., Veiga, F., Serra, J. P., Paiva‐Santos, A. C., & Ribeiro, A. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.08.001 · Cited by 238 · see citing works
Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development
Tibbitts, J., Canter, D., Graff, R., Smith, A. M., & Khawli, L. A. (2015) · mAbs · doi:10.1080/19420862.2015.1115937 · Cited by 210 · see citing works
Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic Proteins
Turner, M. R., & Balu‐Iyer, S. V. (2018) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2018.01.007 · Cited by 177 · see citing works
Subcutaneous Injection Volume of Biopharmaceuticals—Pushing the Boundaries
Mathaes, R., Koulov, A. V., Joerg, S., & Mahler, H. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.05.029 · Cited by 173 · see citing works
Predicting bioavailability of monoclonal antibodies after subcutaneous administration: Open innovation challenge
Sánchez-Félix, M., Burke, M. D., Chen, H. H., Patterson, C. M., & Mittal, S. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.05.009 · Cited by 164 · see citing works
Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic
Seze, J. D., Maillart, É., Guéguen, A., Laplaud, D. A., Michel, L., Thouvenot, É., Zéphir, H., Zimmer, L., Biotti, D., & Liblau, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1004795 · Cited by 162 · see citing works
Subcutaneous Administration of Monoclonal Antibodies: Pharmacology, Delivery, Immunogenicity, and Learnings From Applications to Clinical Development
Davis, J. D., Padros, M. B., Conrado, D. J., Ganguly, S., Guan, X., Hassan, H. E., Hazra, A., Irvin, S. C., Jayachandran, P., Kosloski, M. P., et al. (2023) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3150 · Cited by 119 · see citing works
A novel in vitro method to model the fate of subcutaneously administered biopharmaceuticals and associated formulation components
Kinnunen, H. M., Sharma, V. K., Contreras-Rojas, L. R., Yu, Y., Alleman, C., Sreedhara, A., Fischer, S., Khawli, L. A., Yohe, S. T., Bumbaca, D., et al. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.07.016 · Cited by 119 · see citing works
Accelerating the development of novel technologies and tools for the subcutaneous delivery of biotherapeutics
Collins, D. S., Sánchez-Félix, M., Badkar, A. V., & Mrsny, R. J. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.02.036 · Cited by 113 · see citing works
Challenges and Opportunities in the Delivery of Cancer Therapeutics: Update on Recent Progress
Lorscheider, M., Gaudin, A., Nakhlé, J., Veiman, K.-L., Richard, J., & Chassaing, C. (2020) · Therapeutic Delivery · doi:10.4155/tde-2020-0079 · Cited by 113 · see citing works
A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations
Ghosh, I., Gutka, H. J., Krause, M. E., Clemens, R., & Kashi, R. S. (2023) · mAbs · doi:10.1080/19420862.2023.2205540 · Cited by 108 · see citing works
Vascular Drug Delivery Using Carrier Red Blood Cells: Focus on RBC Surface Loading and Pharmacokinetics
Glassman, P. M., Villa, C. H., Ukidve, A., Zhao, Z., Smith, P. N., Mitragotri, S., Russell, A. J., Brenner, J. S., & Muzykantov, V. R. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12050440 · Cited by 105 · see citing works
Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins
Jarvi, N. L., & Balu‐Iyer, S. V. (2021) · BioDrugs · doi:10.1007/s40259-020-00465-4 · Cited by 105 · see citing works
Understanding Inter-Individual Variability in Monoclonal Antibody Disposition
Thomas, V. A., & Balthasar, J. P. (2019) · Antibodies · doi:10.3390/antib8040056 · Cited by 101 · see citing works
Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins
Smith, A. M., Manoli, H., Jaw, S., Frutoz, K., Epstein, A. L., Khawli, L. A., & Theil, F. (2016) · Journal of Immunology Research · doi:10.1155/2016/2342187 · Cited by 80 · see citing works
Understanding molecular mechanisms of biologics drug delivery and stability from NMR spectroscopy
Phyo, P., Zhao, X. R., Templeton, A. C., Xu, W., Cheung, J. K., & Su, Y. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.02.007 · Cited by 78 · see citing works
The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa
Rosenstock, J., Juneja, R., Beals, J. M., Moyers, J. S., Ilag, L. L., & McCrimmon, R. J. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnad037 · Cited by 83 · see citing works
Comparison of the Efficacy and Safety of Anti-CD20 B Cells Depleting Drugs in Multiple Sclerosis
Cotchett, K. R., Dittel, B. N., & Obeidat, A. Z. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.102787 · Cited by 75 · see citing works
Pharmacokinetics and Clinical Pharmacology of Monoclonal Antibodies in Pediatric Patients
Temrikar, Z. H., Suryawanshi, S., & Meibohm, B. (2020) · Pediatric Drugs · doi:10.1007/s40272-020-00382-7 · Cited by 75 · see citing works
Optimizing the Bioavailability of Subcutaneously Administered Biotherapeutics Through Mechanochemical Drivers
Collins, D. S., Kourtis, L. C., Thyagarajapuram, N. R., Sirkar, R., Kapur, S., Harrison, M. W., Bryan, D. J., Jones, G. B., & Wright, J. M. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2229-9 · Cited by 74 · see citing works
Population pharmacokinetic and exposure‐response analysis of eptinezumab in the treatment of episodic and chronic migraine
Baker, B., Schaeffler, B. A., Béliveau, M., Rubets, I., Pederson, S. M., Trinh, M. M., Smith, J., & Latham, J. A. (2020) · Pharmacology Research & Perspectives · doi:10.1002/prp2.567 · Cited by 67 · see citing works
Influence of physiochemical properties on the subcutaneous absorption and bioavailability of monoclonal antibodies
Datta‐Mannan, A., Estwick, S. A., Zhou, C., Choi, H., Douglass, N. E., Witcher, D. R., Lu, J., Beidler, C. B., & Millican, R. L. (2020) · mAbs · doi:10.1080/19420862.2020.1770028 · Cited by 67 · see citing works
Are chitosan natural polymers suitable as adjuvant/delivery system for anti-tuberculosis vaccines?
Khademi, F., Taheri, R. A., Avarvand, A. Y., Vaez, H., Momtazi‐Borojeni, A. A., & Soleimanpour, S. (2018) · Microbial Pathogenesis · doi:10.1016/j.micpath.2018.05.035 · Cited by 67 · see citing works
Understanding the Monoclonal Antibody Disposition after Subcutaneous Administration using a Minimal Physiologically based Pharmacokinetic Model
Varkhede, N. R., & Forrest, L. M. (2018) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/jpps30028 · Cited by 67 · see citing works
Pediatric physiology in relation to the pharmacokinetics of monoclonal antibodies
Malik, P. R. V., & Edginton, A. N. (2018) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2018.1482278 · Cited by 66 · see citing works
CGRP Monoclonal Antibodies for Migraine: Rationale and Progress
Yuan, H., Lauritsen, C. G., Kaiser, E. A., & Silberstein, S. D. (2017) · BioDrugs · doi:10.1007/s40259-017-0250-5 · Cited by 60 · see citing works
Preclinical Characterization of LY3209590, a Novel Weekly Basal Insulin Fc-Fusion Protein
Moyers, J. S., Hansen, R. J., Day, J. W., Dickinson, C. D., Zhang, C., Ruan, X., Ding, L., Brown, R. M., Baker, H. E., & Beals, J. M. (2022) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.122.001105 · Cited by 61 · see citing works
Fusion of fibroblast growth factor 21 to a thermally responsive biopolymer forms an injectable depot with sustained anti-diabetic action
Gilroy, C. A., Roberts, S., & Chilkoti, A. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.03.015 · Cited by 58 · see citing works
Population pharmacokinetics of subcutaneous infliximab CT‐P13 in Crohn’s disease and ulcerative colitis
Hanžel, J., Bukkems, L. H., Gecse, K. B., D’Haens, G., & Mathôt, R. A. A. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16609 · Cited by 58 · see citing works
Subcutaneous drug delivery from nanoscale systems
Tomasini, L., Ferrere, M., & Nicolas, J. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00161-w · Cited by 59 · see citing works
Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation
Fisher, J. D., Balmert, S. C., Zhang, W., Schweizer, R., Schnider, J. T., Komatsu, C., Dong, L., Erbas, V. E., Unadkat, J. V., Aral, A. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1910701116 · Cited by 58 · see citing works
Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial
Westhovens, R., Wiland, P., Zawadzki, M., Ivanova, D., Kasay, A. B., El-Khouri, E. C., Balázs, É., Shevchuk, S. V., Елисеева, Л. В., Stanislavchuk, M., et al. (2020) · Lara D. Veeken · doi:10.1093/rheumatology/keaa580 · Cited by 57 · see citing works
Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins
Zou, P., Wang, F., Wang, J., Lu, Y., Tran, D. C., & Seo, S. K. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.06.038 · Cited by 55 · see citing works
Pharmacokinetic Variability of Therapeutic Antibodies in Humans: A Comprehensive Review of Population Pharmacokinetic Modeling Publications
Bensalem, A., & Ternant, D. (2020) · Clinical Pharmacokinetics · doi:10.1007/s40262-020-00874-2 · Cited by 55 · see citing works
Physiologically based pharmacokinetic models of small molecules and therapeutic antibodies: a mini‐review on fundamental concepts and applications
Ferl, G. Z., Theil, F., & Wong, H. (2016) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1994 · Cited by 54 · see citing works
Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies
Borte, M., Kriván, G., Dérfalvi, B., Maródi, L., Harrer, T., Jolles, S. R. A., Bourgeois, C., Engl, W., Leibl, H., McCoy, B., et al. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12866 · Cited by 54 · see citing works
Clinical evaluation of large volume subcutaneous injection tissue effects, pain, and acceptability in healthy adults
Woodley, W. D., Morel, D. R., Sutter, D. E., Pettis, R. J., & Bolick, N. G. (2021) · Clinical and Translational Science · doi:10.1111/cts.13109 · Cited by 49 · see citing works
Hyaluronidase-powered microneedles for significantly enhanced transdermal delivery efficiency
Hu, W., Peng, T., Huang, Y., Ren, T., Chen, H., Chen, Y., Feng, D., Wu, C., & Pan, X. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.046 · Cited by 50 · see citing works
Transport and lymphatic uptake of monoclonal antibodies after subcutaneous injection
Rahimi, E., Aramideh, S., Han, D., Gómez, H., & Ardekani, A. M. (2021) · Microvascular Research · doi:10.1016/j.mvr.2021.104228 · Cited by 47 · see citing works
Pharmacokinetic Considerations for Antibody-Drug Conjugates against Cancer
Malik, P. R. V., Phipps, C. J., Edginton, A. N., & Blay, J. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2259-3 · Cited by 47 · see citing works
Population Pharmacokinetics and Target Engagement of Natalizumab in Patients With Multiple Sclerosis
Muralidharan, K. K., Kuesters, G. M., Plavina, T., Subramanyam, M., Mikol, D. D., Gopal, S., & Nestorov, I. A. (2017) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.894 · Cited by 45 · see citing works
A comparable study of polyglycolic acid's degradation on macrophages' activation
Zhang, J., Xie, B., Xi, Z., Zhao, L., Cen, L., & Yang, Y. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110574 · Cited by 47 · see citing works
Real‐world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel diseases
Volkers, A., Straatmijer, T., Duijvestein, M., Sales, A., Levran, A., van Schaik, F. D. M., Maljaars, J., Gecse, K. B., Ponsioen, C. Y., Grootjans, J., et al. (2022) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17153 · Cited by 44 · see citing works
Advanced Formulations/Drug Delivery Systems for Subcutaneous Delivery of Protein-Based Biotherapeutics
Lou, H., Feng, M., & Hageman, M. J. (2022) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2022.08.036 · Cited by 42 · see citing works
Population Pharmacokinetic Analysis and Exploratory Exposure–Bleeding Rate Relationship of Emicizumab in Adult and Pediatric Persons with Hemophilia A
Retout, S., Schmitt, C., Petry, C., Mercier, F., & Frey, N. (2020) · Clinical Pharmacokinetics · doi:10.1007/s40262-020-00904-z · Cited by 40 · see citing works
Hematopoietic cells as site of first-pass catabolism after subcutaneous dosing and contributors to systemic clearance of a monoclonal antibody in mice
Richter, W. F., Christianson, G. J., Frances, N., Grimm, H. P., Proetzel, G., & Roopenian, D. C. (2018) · mAbs · doi:10.1080/19420862.2018.1458808 · Cited by 39 · see citing works
Self-citation
Antibody–Drug Conjugates—Evolution and Perspectives
Chiş, A. A., Dobrea, C. M., Arseniu, A. M., Frum, A., Rus, L. L., Cormoș, G., Georgescu, C., Morgovan, C., Butucă, A., Gligor, F. G., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25136969 · Cited by 40 · see citing works
Peptide loaded polymeric nanoparticles by non-aqueous nanoprecipitation
Zada, M. H., Rottenberg, Y., & Domb, A. J. (2022) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2022.05.007 · Cited by 37 · see citing works
Advancing Subcutaneous Dosing Regimens for Biotherapeutics: Clinical Strategies for Expedited Market Access
Bittner, B., & Schmidt, J. (2023) · BioDrugs · doi:10.1007/s40259-023-00626-1 · Cited by 37 · see citing works
Ti3C2 (MXene), an advanced carrier system: role in photothermal, photoacoustic, enhanced drugs delivery and biological activity in cancer therapy
Deb, V. K., & Jain, U. (2024) · Drug Delivery and Translational Research · doi:10.1007/s13346-024-01572-3 · Cited by 37 · see citing works
Predicting monoclonal antibody pharmacokinetics following subcutaneous administration via whole-body physiologically-based modeling
Hu, S., & D’Argenio, D. Z. (2020) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-020-09691-3 · Cited by 38 · see citing works
Systematic Review of Device Parameters and Design of Studies Bridging Biologic-Device Combination Products Using Prefilled Syringes and Autoinjectors
Hu, P., Wang, J., Florian, J., Shatzer, K., Stevens, A. M., Gertz, J. M., Ji, P., Huang, S. M., Zineh, I., & Wang, Y. (2020) · The AAPS Journal · doi:10.1208/s12248-020-0433-8 · Cited by 36 · see citing works
Safety, tolerability and pharmacokinetics of subcutaneous and intravenous anifrolumab in healthy volunteers
Tummala, R., Rouse, T., Berglind, A., & Santiago, L. (2018) · Lupus Science & Medicine · doi:10.1136/lupus-2017-000252 · Cited by 34 · see citing works
Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Model Development
Zheng, F., Hou, P., Corpstein, C. D., Xing, L., & Li, T. (2021) · Pharmaceutical Research · doi:10.1007/s11095-021-03032-w · Cited by 34 · see citing works
Development of Therapeutic Proteins for a New Subcutaneous Route of Administration After the Establishment of Intravenous Dosages: A Systematic Review
Xu, Z., Leu, J. H., Xu, Y. C., Nnane, I. P., Liva, S. G., Wang‐Lin, S. X., Kudgus-Lokken, R., Vermeulen, A., & Ouellet, D. (2022) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2823 · Cited by 34 · see citing works
The Contribution of Liver Sinusoidal Endothelial Cells to Clearance of Therapeutic Antibody
James, B. H., Papakyriacou, P., Gardener, M. J., Gliddon, L., Weston, C. J., & Lalor, P. F. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2021.753833 · Cited by 32 · see citing works
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers
Costa, M. B., Picon, P. D., Sander, G. B., Cuní, H. N., Silva, C. V., Meireles, R. P., de Góes, A. C. M. A., Batoreu, N. M., Maia, M. D. L. D. S., de Albuquerque, E. M., et al. (2018) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-017-0192-z · Cited by 32 · see citing works
A novel antigen of Mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity
Khademi, F., Derakhshan, M., Avarvand, A. Y., Najafi, A., & Tafaghodi, M. (2018) · Microbial Pathogenesis · doi:10.1016/j.micpath.2018.10.023 · Cited by 32 · see citing works
Prediction of subcutaneous drug absorption - do we have reliable data to design a simulated interstitial fluid?
Torres-Terán, I., Venczel, M., & Klein, S. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121257 · Cited by 30 · see citing works
Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Sensitivity Analysis
Hou, P., Zheng, F., Corpstein, C. D., Xing, L., & Li, T. (2021) · Pharmaceutical Research · doi:10.1007/s11095-021-03062-4 · Cited by 29 · see citing works
Relative Bioavailability of a Single Dose of Belimumab Administered Subcutaneously by Prefilled Syringe or Autoinjector in Healthy Subjects
Struemper, H., Murtaugh, T., Gilbert, J., Barton, M. E., Fire, J., Groark, J., Fox, N. L., Roth, D. A., & Gordon, D. N. (2015) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.219 · Cited by 28 · see citing works
Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes
Jayakrishnapillai, P. V., Nair, S. V., & Kamalasanan, K. (2017) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2017.02.017 · Cited by 28 · see citing works
RETRACTED ARTICLE: Pharmacokinetics, Biodistribution, and Anti-Angiogenesis Efficacy of Diamino Propane Tetraiodothyroacetic Acid-conjugated Biodegradable Polymeric Nanoparticle
Li, W., Yalçın, M., Bharali, D. J., Lin, Q., Godugu, K., Fujioka, K., Keating, K. A., & Mousa, S. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-44979-6 · Cited by 28 · see citing works
Retracted
Impact of Pre-Existing or Induced Anti-PEG IgM on the Pharmacokinetics of Peginterferon Alfa-2a (Pegasys) in Mice
Elsadek, N. E., Hondo, E., Shimizu, T., Takata, H., Lila, A. S. A., Emam, S. E., Ando, H., Ishima, Y., & Ishida, T. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00366 · Cited by 27 · see citing works
Multiscale pharmacokinetic modeling of systemic exposure of subcutaneously injected biotherapeutics
Zheng, F., Hou, P., Corpstein, C. D., Park, K., & Li, T. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.07.043 · Cited by 28 · see citing works
Impact of Precipitation of Antibody Therapeutics After Subcutaneous Injection on Pharmacokinetics and Immunogenicity
Kinderman, F. S., Yerby, B., Jawa, V., Joubert, M. K., Joh, N. H., Malella, J., Herskovitz, J., Xie, J., Ferbas, J., & McBride, H. J. (2019) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2019.01.015 · Cited by 28 · see citing works
Electrostatic interactions modulate the differential aggregation propensities of IgG1 and IgG4P antibodies and inform charged residue substitutions for improved developability
Heads, J. T., Lamb, R., Kelm, S., Adams, R., Elliott, P., Tyson, K. L., Topia, S., West, S. M., Nan, R., Turner, A. V., et al. (2019) · Protein Engineering Design and Selection · doi:10.1093/protein/gzz046 · Cited by 27 · see citing works
Key considerations in designing CRISPR/Cas9-carrying nanoparticles for therapeutic genome editing
Xu, Y., Liu, R., & Dai, Z. (2020) · Nanoscale · doi:10.1039/d0nr05452f · Cited by 27 · see citing works
A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity
Zhang, L., Navaratna, T. A., & Thurber, G. M. (2016) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6b00209 · Cited by 26 · see citing works
Population Pharmacokinetics and Exposure‐Response Relationship of Intravenous and Subcutaneous Abatacept in Patients With Rheumatoid Arthritis
Li, X., Roy, A., & Murthy, B. (2018) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1308 · Cited by 27 · see citing works
Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates
Qin, M., Wang, L., Wu, D., Williams, C. K., Xu, D., Kranz, E. O., Guo, Q., Guan, J., Vinters, H. V., Lee, Y., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03132 · Cited by 27 · see citing works
Evaluation of Evolocumab (AMG 145), a Fully Human Anti‐PCSK9 IgG2 Monoclonal Antibody, in Subjects With Hepatic Impairment
Gibbs, J. P., Slatter, J. G., Egbuna, O. I., Geller, M. L., Hamilton, L. J., Dias, C. S., Xu, R., Johnson, J., Wasserman, S. M., & Emery, M. G. (2016) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.832 · Cited by 26 · see citing works
A Two-Pore Physiologically Based Pharmacokinetic Model to Predict Subcutaneously Administered Different-Size Antibody/Antibody Fragments
Li, Z., Yu, X., Li, Y.-Y., Verma, A., Chang, H., & Shah, D. K. (2021) · The AAPS Journal · doi:10.1208/s12248-021-00588-8 · Cited by 25 · see citing works
Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction
Kole, M. J., Wessell, A. P., Ugiliweneza, B., Cannarsa, G. J., Fortuny, E. M., Stokum, J. A., Shea, P., Chryssikos, T. J., Khattar, N. K., Crabill, G. A., et al. (2020) · Neurosurgery · doi:10.1093/neuros/nyaa473 · Cited by 25 · see citing works
Oligomerization, albumin binding and catabolism of therapeutic peptides in the subcutaneous compartment: An investigation on lipidated GLP-1 analogs
Gallo, M. L., Vanni, D., Esposito, S., Alaimo, N., Orvieto, F., Rulli, F., Missineo, A., Caretti, F., Bonelli, F., Veneziano, M., et al. (2022) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2021.114566 · Cited by 24 · see citing works
Recent advances in identifying and utilizing metabolites of selected doping agents in human sports drug testing
Thevis, M., Piper, T., & Thomas, A. (2021) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2021.114312 · Cited by 24 · see citing works
Subcutaneous Injection Performance in Yucatan Miniature Pigs with and without Human Hyaluronidase and Auto-injector Tolerability in Humans
Shi, G. H., Connor, R., Collins, D. S., & Kang, D. W. (2021) · AAPS PharmSciTech · doi:10.1208/s12249-020-01880-0 · Cited by 22 · see citing works
Subcutaneous Site-of-Absorption Study with the Monoclonal Antibody Tocilizumab in Minipigs: Administration Behind Ear Translates Best to Humans
Richter, W. F., Grimm, H.-P., Gouy, M.-H., Søgaard, S., Kreuzer, C., Wessels, U., Draganov, D. I., Muenzer, C., & Hoche, T. (2020) · The AAPS Journal · doi:10.1208/s12248-020-00446-z · Cited by 22 · see citing works
Self-citation
Dispersive effects and focused biodistribution of recombinant human hyaluronidase PH20: A locally acting and transiently active permeation enhancer
Kang, D. W., Bittner, B., Sugarman, B. J., Zepeda, M. L., & Printz, M. A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254765 · Cited by 21 · see citing works
Probing the subcutaneous absorption of a PEGylated FUD peptide nanomedicine via in vivo fluorescence imaging
Zbyszynski, P., Toraason, I., Repp, L., & Kwon, G. S. (2019) · Nano Convergence · doi:10.1186/s40580-019-0192-3 · Cited by 21 · see citing works
Modeling the subcutaneous pharmacokinetics of antibodies co‐administered with rHuPH20
Nolan, R. P., & Printz, M. A. (2024) · Clinical and Translational Science · doi:10.1111/cts.13788 · Cited by 19 · see citing works
Intra-articular injection of biologic anti-rheumatic drugs enhances local exposure to the joint-draining lymphatics
Lam, A. D., Cao, E., Leong, N. J., Gracia, G., Porter, C. J. H., Feeney, O. M., & Trevaskis, N. L. (2022) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2022.02.014 · Cited by 20 · see citing works
Lymphatic uptake of biotherapeutics through a 3D hybrid discrete-continuum vessel network in the skin tissue
Han, D., Li, C., Araimdeh, S., Sree, V. D., Rahimi, E., Tepole, A. B., & Ardekani, A. M. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.12.045 · Cited by 19 · see citing works
Golimumab Dried Blood Spot Analysis (GOUDA): a Prospective Trial Showing Excellent Correlation with Venepuncture Samples and More Detailed Pharmacokinetic Information
Detrez, I., Schops, G., Lefrère, J., Tops, S., Assche, G. V., Vermeire, S., Moerkercke, W. V., Ferrante, M., & Gils, A. (2018) · The AAPS Journal · doi:10.1208/s12248-018-0282-x · Cited by 19 · see citing works
Monoclonal Antibody Monitoring: Clinically Relevant Aspects, A Systematic Critical Review
Regazzi, M. B., Golay, J., & Molinaro, M. (2019) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000000681 · Cited by 19 · see citing works
Non-clinical Safety Evaluation of Biotherapeutics – Challenges, Opportunities and new Insights
Blaich, G., Baumann, A., Kronenberg, S., de Haan, L., Ulrich, P. C., Richter, W., Tibbitts, J., Chivers, S., Tarcsa, E., Caldwell, R. G., et al. (2016) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2016.08.012 · Cited by 18 · see citing works
Self-citation
Intramuscular and subcutaneous administration of antiretroviral drugs, compared with oral, enhances delivery to lymphoid tissues in BALB/c mice
Dyavar, S. R., Kumar, S., Gautam, N., Podany, A. T., Winchester, L. C., Weinhold, J. A., Mykris, T. M., Nallasamy, P., Alnouti, Y., & Fletcher, C. V. (2021) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkab228 · Cited by 17 · see citing works
Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging
Vergara, I., Castillo, E., Romero-Piña, M., Torres-Viquez, I., Paniagua, D., Boyer, L., Alagon, A. C., & Medina, L. A. (2016) · Toxins · doi:10.3390/toxins8040085 · Cited by 17 · see citing works
Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA: Subcutaneous administration.
Khademi, F., Avarvand, A. Y., Derakhshan, M., Najafi, A., & Tafaghodi, M. (2019) · PubMed Central · doi:10.22038/ijbms.2019.33962.8079 · Cited by 17 · see citing works
Predicting human subcutaneous bioavailability of monoclonal antibodies using an integrated in-vitro/in-silico approach
Hanafy, B. I., Trayton, I., Sundqvist, M., Caldwell, J. G., Mody, N., Day, K., & Mazza, M. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.02.022 · Cited by 16 · see citing works
Fluorescent Tracers for In Vivo Imaging of Lymphatic Targets
Russell, P. S., Velivolu, R., Maldonado-Zimbrón, V. E., Hong, J., Kavianinia, I., Hickey, A. J., Windsor, J. A., & Phillips, A. R. J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.952581 · Cited by 16 · see citing works
MPET 2 : a multi-network poroelastic and transport theory for predicting absorption of monoclonal antibodies delivered by subcutaneous injection
Wang, H., Hu, T., Leng, Y., de Lucio, M., & Gómez, H. (2023) · Drug Delivery · doi:10.1080/10717544.2022.2163003 · Cited by 16 · see citing works
Injectable hydrogel formulations: Design, synthesis and applications for subcutaneous delivery – A comprehensive review
Sarvepalli, S., & Kandagatla, H. P. (2024) · European Polymer Journal · doi:10.1016/j.eurpolymj.2024.113610 · Cited by 16 · see citing works
Nanocapsule assemblies as effective enzyme delivery systems against hyperuricemia
Xiong, H., Zhou, Y., Zhou, Q., He, D., Deng, X., Sun, Q., & Zhang, J. (2016) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2016.02.010 · Cited by 16 · see citing works
Tissue barriers and novel approaches to achieve hepatoselectivity of subcutaneously-injected insulin therapeutics
Shao, J., Zaro, J. L., & Shen, W. (2016) · Tissue Barriers · doi:10.1080/21688370.2016.1156804 · Cited by 16 · see citing works

Pharmacokinetic Modeling of the Subcutaneous Absorption of Therapeutic Proteins
Kagan, L. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.059121 · Cited by 92 · see citing works
Role of Lymphatic System in Subcutaneous Absorption of Therapeutic Proteins
Lin, J. H., & Wang, W. (2015) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse541
Lymphatic Transport and Catabolism of Therapeutic Proteins after Subcutaneous Administration to Rats and Dogs
Wang, W., Chen, N., Shen, X., Cunningham, P. K., Fauty, S. E., Michel, K. B., Wang, B., Hong, X., Adreani, C. M., Nunes, C. N., et al. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.043604 · Cited by 86 · see citing works
Mechanistic Determinants of Biotherapeutics Absorption Following SC Administration
Richter, W. F., Bhansali, S. G., & Morris, M. E. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9367-0 · Cited by 377 · see citing works
Self-citation
Transport and Lymphatic Uptake of Biotherapeutics Through Subcutaneous Injection
Han, D., Rahimi, E., Aramideh, S., & Ardekani, A. M. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.09.045 · Cited by 28 · see citing works

Authors: Richter, W. F., & Jacobsen, B.
Affiliations: F. Hoffmann-La Roche AG (CH)
ORCID: Richter, Wolfgang F.
Jacobsen, Björn
Venue: Drug Metabolism and Disposition
Publisher: Elsevier BV
Published: 2014-11
Volume: 42
Issue: 11
Pages: 1881-1889
ISSN: 0090-9556 (ISSN-L)
DOI: 10.1124/dmd.114.059238
OpenAlex: W2111354448
Cited by: 235
References: 62
Citations by year: 2026: 16 · 2025: 18 · 2024: 28 · 2023: 19 · 2022: 32 · 2021: 28 · 2020: 31 · 2019: 17 · 2018: 18 · 2017: 10 · 2016: 12 · 2015: 6
FWCI: 7.29
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Drug Metabolism and Disposition (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
Keywords: subcutaneous absorption, biologic therapy, monoclonal antibodies, pharmacokinetics, lymphatic absorption, subcutaneous tissue, neonatal Fc receptor, IgG, bioavailability, species differences
MeSH terms: Animals, Biological Availability, Biological Products, Humans, Skin Absorption, Infusions, Subcutaneous

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Subcutaneous Absorption of Biotherapeutics: Knowns and Unknowns

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks