Physiologically based pharmacokinetic models of small molecules and therapeutic antibodies: a mini‐review on fundamental concepts and applications
Abstract
The mechanisms of absorption, distribution, metabolism and elimination of small and large molecule therapeutics differ significantly from one another and can be explored within the framework of a physiologically based pharmacokinetic (PBPK) model. This paper briefly reviews fundamental approaches to PBPK modeling, in which drug kinetics within tissues and organs are explicitly represented using physiologically meaningful parameters. The differences in PBPK models applied to small/large molecule drugs are highlighted, thus elucidating differences in absorption, distribution and elimination properties between these two classes of drugs in a systematic manner. The absorption of small and large molecules differs with respect to their common extravascular routes of delivery (oral versus subcutaneous). The role of the lymphatic system in drug distribution, and the involvement of tissues as sites of elimination (through catabolism and target mediated drug disposition) are unique features of antibody distribution and elimination that differ from small molecules, which are commonly distributed into the tissues but are eliminated primarily by liver metabolism. Fundamental differences exist in the ability to predict human pharmacokinetics based upon preclinical data due to differing mechanisms governing small and large molecule disposition. These differences have influence on the evolving utilization of PBPK modeling in the discovery and development of small and large molecule therapeutics. Copyright © 2015 John Wiley & Sons, Ltd.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
PBPK modeling has been adapted in mAb scaling.
“Recently, physiologically based PK (PBPK) modeling has been adapted in mAb scaling despite its complexity.29”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [29]
Cites
Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169 · see citing works
Elements of chemical reaction engineering
Fogler, H. S. (1987) · Chemical Engineering Science · doi:10.1016/0009-2509(87)80130-6 · Cited by 3,110 · see citing works
FcRn: the neonatal Fc receptor comes of age
Roopenian, D. C., & Akilesh, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2155 · Cited by 2,346 · see citing works
Clinical importance of the cytochromes P450
Nebert, D. W., & Russell, D. W. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11203-7 · Cited by 1,416 · see citing works
The Original Michaelis Constant: Translation of the 1913 Michaelis-Menten Paper
Johnson, K., & Goody, R. (2011) · Biochemistry · doi:10.1021/bi201284u · Cited by 1,377 · see citing works
Rodgers, T., & Rowland, M. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20502 · Cited by 949 · see citing works
Williams, J. A., Hyland, R., Jones, B., Smith, D. A., Hurst, S. I., Goosen, T. C., Peterkin, V. C., Koup, J. R., & Ball, S. E. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.000794 · Cited by 929 · see citing works
Rodgers, T., Leahy, D., & Rowland, M. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20322 · Cited by 776 · see citing works
Waldmann, T. A., & Strober, W. (2015) · Chemical immunology/Fortschritte der Allergielehre/Progress in allergy/Chemical immunology and allergy · doi:10.1159/000385919 · Cited by 723 · see citing works
Junghans, R. P., & Anderson, C. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5512 · Cited by 685 · see citing works
Predicting the Impact of Physiological and Biochemical Processes on Oral Drug Bioavailability
Agoram, B., Woltosz, W. S., & Bolger, M. B. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00179-x · Cited by 651 · see citing works
Physiologically Based Pharmacokinetic Modeling: Principles and Applications
Gerlowski, L. E., & Jain, R. K. (1983) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600721003 · Cited by 580 · see citing works
Poulin, P., & Theil, F. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10005 · Cited by 568 · see citing works
Self-citationTransport of macromolecules across microvascular walls: the two-pore theory
Rippe, B., & Haraldsson, B. S. (1994) · Physiological Reviews · doi:10.1152/physrev.1994.74.1.163 · Cited by 564 · see citing works
Jones, H., Chen, Y., Gibson, C., Heimbach, T., Parrott, N., Peters, S., Snoeys, J., Upreti, V., Zheng, M., & Hall, S. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.37 · Cited by 488 · see citing works
Abnormally short serum half‐lives of IgG in β2‐microglobulin‐deficient mice
Ghetie, V. F., Hubbard, J. G., Kim, J., Tsen, M. F., Lee, Y., & Ward, E. S. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260327 · Cited by 469 · see citing works
A compartmental absorption and transit model for estimating oral drug absorption
Yu, L. X., & Amidon, G. L. (1999) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(99)00147-7 · Cited by 455 · see citing works
A Theoretical Model of γ-Globulin Catabolism
Brambell, F. W. R., Hemmings, W. A., & MORRIS, I. G. (1964) · Nature · doi:10.1038/2031352a0 · Cited by 451 · see citing works
Shah, D. K., & Betts, A. M. (2011) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-011-9232-2 · Cited by 424 · see citing works
Species similarities and differences in pharmacokinetics.
Lin, J. H. (1995) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)06742-x · Cited by 397 · see citing works
Dedrick, R. L. (1973) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01059667 · Cited by 397 · see citing works
Hirayama, C. (1968) · SEIBUTSU BUTSURI KAGAKU · doi:10.2198/sbk.13.201 · Cited by 350 · see citing works
Increased clearance of IgG in mice that lack β2‐microglobulin: possible protective role of FcRn
Israel, E. J., Wilsker, D. F., Hayes, K. C., Schoenfeld, D., & Simister, N. E. (1996) · Immunology · doi:10.1046/j.1365-2567.1996.d01-775.x · Cited by 334 · see citing works
Garg, A., & Balthasar, J. P. (2007) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-007-9065-1 · Cited by 329 · see citing works
Renal Transporters in Drug Development
Morrissey, K. M., STOCKER, S. L., Wittwer, M., Xu, L., & Giacomini, K. M. (2012) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140317 · Cited by 326 · see citing works
Pharmacokinetics of monoclonal immunoglobulin G1, F(ab')2, and Fab' in mice.
Covell, D. G., Barbet, J., Holton, O. D., BLACK, C. D. V., Parker, R. J., & Weinstein, J. N. (1986) · PubMed · Cited by 311 · see citing works
Deng, R., Iyer, S., Theil, F.-P., Mortensen, D. L., Fielder, P. J., & Prabhu, S. (2011) · mAbs · doi:10.4161/mabs.3.1.13799 · Cited by 285 · see citing works
Self-citationBaxter, L. T., Zhu, H. J., Mackensen, D. G., & Jain, R. K. (1994) · PubMed · Cited by 280 · see citing works
Reduced elimination of IgG antibodies by engineering the variable region
Igawa, T., Tsunoda, H., Tachibana, T., Maeda, A., Mimoto, F., Moriyama, C., Nanami, M., Sekimori, Y., Nabuchi, Y., Aso, Y., et al. (2010) · Protein Engineering Design and Selection · doi:10.1093/protein/gzq009 · Cited by 265 · see citing works
De Buck, S. S., Sinha, V. K., Fenu, L. A., Nijsen, M. J., Mackie, C. E., & Gilissen, R. A. H. J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015644 · Cited by 256 · see citing works
Yeung, Y. A., Leabman, M. K., Marvin, J. S., Qiu, J., Adams, C. W., Lien, S., Starovasnik, M. A., & Lowman, H. B. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804182 · Cited by 237 · see citing works
Subcutaneous Absorption of Biotherapeutics: Knowns and Unknowns
Richter, W. F., & Jacobsen, B. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.059238 · Cited by 235 · see citing works
Bischoff, K. B., & Dedrick, R. L. (1968) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600570814 · Cited by 211 · see citing works
Whole-body physiologically based pharmacokinetic models
Nestorov, I. A. (2007) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.3.2.235 · Cited by 188 · see citing works
Baxter, L. T., Zhu, H. J., Mackensen, D. G., Butler, W. F., & Jain, R. K. (1995) · PubMed · Cited by 179 · see citing works
Second-generation minimal physiologically-based pharmacokinetic model for monoclonal antibodies
Cao, Y., Balthasar, J. P., & Jusko, W. J. (2013) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-013-9332-2 · Cited by 161 · see citing works
Whole body physiologically-based pharmacokinetic models: their use in clinical drug development
Edginton, A. N., Theil, F., Schmitt, W., & Willmann, S. (2008) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.4.9.1143 · Cited by 154 · see citing works
Self-citationTranscytosis and Catabolism of Antibody
Ghetie, V. F., & Ward, E. S. (2002) · Immunologic Research · doi:10.1385/ir:25:2:097 · Cited by 150 · see citing works
Parrott, N. J., Lukacova, V., Fraczkiewicz, G., & Bolger, M. B. (2009) · The AAPS Journal · doi:10.1208/s12248-008-9079-7 · Cited by 150 · see citing works
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-citationFerl, G. Z., Wu, A. M., & DiStefano, J. J. (2005) · Annals of Biomedical Engineering · doi:10.1007/s10439-005-7410-3 · Cited by 144 · see citing works
Self-citationLi, B., Tesar, D. B., Boswell, C. A., Cahaya, H. S., Wong, A., Zhang, J., Meng, Y. G., Eigenbrot, C. W., Pantua, H., Diao, J., et al. (2014) · mAbs · doi:10.4161/mabs.29809 · Cited by 122 · see citing works
Yeo, K. R., Walsky, R. L., Jamei, M., Rostami‐Hodjegan, A., & Tucker, G. T. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.04.008 · Cited by 118 · see citing works
Jones, H. M., Gardner, I. B., Collard, W. T., Stanley, P. J., Oxley, P., Hosea, N. A., Plowchalk, D., Gernhardt, S., Lin, J., Dickins, M., et al. (2011) · Clinical Pharmacokinetics · doi:10.2165/11539680-000000000-00000 · Cited by 110 · see citing works
Davda, J. P., Jain, M., Batra, S. K., Gwilt, P. R., & Robinson, D. H. (2007) · International Immunopharmacology · doi:10.1016/j.intimp.2007.10.023 · Cited by 107 · see citing works
Chen, Y., & Balthasar, J. P. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9395-9 · Cited by 105 · see citing works
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
Physiologically based pharmacokinetic model for T84.66: A monoclonal anti-CEA antibody
Urva, S., Yang, V. C.-M., & Balthasar, J. P. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21918 · Cited by 105 · see citing works
Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?
Bouzom, F., Ball, K., Perdaems, N., & Walther, B. (2012) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1767 · Cited by 99 · see citing works
Andersen, M. E. (1995) · Toxicology Letters · doi:10.1016/0378-4274(95)03355-o · Cited by 94 · see citing works
Kenanova, V. E., Olafsen, T., Williams, L. E., Ruel, N. H., Longmate, J., Yazaki, P. J., Shively, J. E., Colcher, D. M., Raubitschek, A. A., & Wu, A. M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-0454 · Cited by 93 · see citing works
FcRn: From Molecular Interactions to Regulation of IgG Pharmacokinetics and Functions
Challa, D. K., Velmurugan, R., Ober, R. J., & Ward, E. S. (2014) · Current topics in microbiology and immunology · doi:10.1007/978-3-319-07911-0_12 · Cited by 84 · see citing works
A Physiologically Based Pharmacokinetic Model of Docetaxel Disposition: from Mouse to Man
Bradshaw‐Pierce, E. L., Eckhardt, S., & Gustafson, D. L. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2362 · Cited by 83 · see citing works
Igari, Y., Sugiyama, Y., Awazu, S., & Hanano, M. (1982) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01059183 · Cited by 80 · see citing works
Lin, J., Sugiyama, Y., Awazu, S., & Hanano, M. (1982) · Journal of pharmacokinetics and biopharmaceutics · doi:10.1007/bf01062545 · Cited by 79 · see citing works
Some fundamental considerations of the applications of pharmacokinetics to cancer chemotherapy.
Bischoff, K. B. (1975) · PubMed · Cited by 75 · see citing works
Xia, B., Heimbach, T., Gollen, R., Nanavati, C., & He, H. (2013) · The AAPS Journal · doi:10.1208/s12248-013-9505-3 · Cited by 68 · see citing works
Li, L., Gardner, I. B., Dostálek, M., & Jamei, M. (2014) · The AAPS Journal · doi:10.1208/s12248-014-9640-5 · Cited by 63 · see citing works
A two-tiered physiologically based model for dually labeled single-chain Fv-Fc antibody fragments
Ferl, G. Z., Kenanova, V. E., Wu, A. M., & DiStefano, J. J. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0072 · Cited by 63 · see citing works
Self-citationTHE ABSORPTION, DISTRIBUTION, AND ELIMINATION OF ETHYL ETHER
Haggard, H. W. (1924) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)85258-9 · Cited by 61 · see citing works
Physiologically-based pharmacokinetic modeling for absorption, transport, metabolism and excretion
Pang, K. S., & Durk, M. R. (2010) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-010-9185-x · Cited by 59 · see citing works
Friedrich, S. W., Linz, S. C., Stoll, B. R., Baxter, L. T., Munn, L. L., & Jain, R. K. (2002) · Neoplasia · doi:10.1038/sj.neo.7900260 · Cited by 59 · see citing works
Physiologically based pharmacokinetic analyses of simple mixtures.
Krishnan, K., M.A., H. J. C. I., & Andersen, M. E. (1994) · Environmental Health Perspectives · doi:10.1289/ehp.94102s9151 · Cited by 58 · see citing works
Kumar, V., Prasad, B., Patilea-Vrana, G., Gupta, A., Salphati, L., Evers, R., Hop, C. E. C. A., & Unadkat, J. D. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.061614 · Cited by 56 · see citing works
Applications of physiologic pharmacokinetic modeling in carcinogenic risk assessment.
Krewski, D. R., Withey, J. R., Ku, L. F., & Andersen, M. E. (1994) · Environmental Health Perspectives · doi:10.1289/ehp.94102s1137 · Cited by 52 · see citing works
Kletting, P., Kull, T. J., Bunjes, D. W., Mahren, B., Luster, M., Reske, S. N., & Glatting, G. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.109.067546 · Cited by 51 · see citing works
Gurbaxani, B. M., Dostálek, M., & Gardner, I. B. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.05.008 · Cited by 50 · see citing works
Clausen, J., & Bickel, M. H. (1993) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600820402 · Cited by 46 · see citing works
Fronton, L., Pilari, S., & Huisinga, W. (2014) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-014-9349-1 · Cited by 44 · see citing works
Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model
Kletting, P., Bunjes, D. W., Reske, S. N., & Glatting, G. (2009) · Journal of Nuclear Medicine · doi:10.2967/jnumed.108.054189 · Cited by 44 · see citing works
Potential and limitations of radioimmunodetection and radioimmunotherapy with monoclonal antibodies.
Zhu, H., Baxter, L. T., & Jain, R. K. (1997) · PubMed · Cited by 43 · see citing works
Tumor pretargeting for radioimmunodetection and radioimmunotherapy.
Zhu, H. J., Jain, R. K., & Baxter, L. T. (1998) · PubMed · Cited by 41 · see citing works
Prediction of drug distribution in vivo on the basis of in vitro binding data
Schuhmann, G., Fichtl, B., & Kurz, H. (1987) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2510080109 · Cited by 40 · see citing works
Chiang, P., & Wong, H. (2013) · The AAPS Journal · doi:10.1208/s12248-013-9519-x · Cited by 37 · see citing works
Self-citationLaplanche, R., Meno‐Tetang, G. M. L., & Kawai, R. (2007) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-007-9051-7 · Cited by 36 · see citing works
Shah, D. K., & Balthasar, J. P. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.01.038 · Cited by 25 · see citing works
Heiskanen, T., Heiskanen, T., & Kairemo, K. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209787581968 · Cited by 23 · see citing works
Wong, H., Theil, F., Cui, Y., Marsters, J. C., Khojasteh, S. C., Vernillet, L., La, H., Song, X., Wang, H., Morinello, E. J., et al. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.032680 · Cited by 21 · see citing works
Self-citationPredictive Physiologically Based Pharmacokinetic Model for Antibody-Directed Enzyme Prodrug Therapy
Fang, L., & Sun, D. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.019182 · Cited by 20 · see citing works
Flagged first, then by citations
1 of the 80 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Separating host and microbiome contributions to drug pharmacokinetics and toxicity
Zimmermann, M., Zimmermann‐Kogadeeva, M., Wegmann, R., & Goodman, A. L. (2019) · Science · doi:10.1126/science.aat9931 · Cited by 427 · see citing works
Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development
Ovacik, M., & Lin, K. (2018) · Clinical and Translational Science · doi:10.1111/cts.12567 · Cited by 299 · see citing works
Systems pharmacology – Towards the modeling of network interactions
Danhof, M. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.04.027 · Cited by 120 · see citing works
Zheng, P., Li, J., & Kros, J. M. (2017) · Medicinal Research Reviews · doi:10.1002/med.21463 · Cited by 97 · see citing works
Sego, T. J., Aponte-Serrano, J. O., Gianlupi, J. F., Heaps, S. R., Breithaupt, K., Brusch, L., Crawshaw, J. R., Osborne, J. M., Quardokus, E. M., Plemper, R. K., et al. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008451 · Cited by 69 · 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
Begum, N. J., Glatting, G., Wester, H., Eiber, M., Beer, A. J., & Kletting, P. (2019) · Scientific Reports · doi:10.1038/s41598-019-56603-8 · Cited by 63 · see citing works
Aborig, M., Malik, P. R. V., Nambiar, S., Chelle, P., Darko, J., Mutsaers, A. J., Edginton, A. N., Fleck, A., Osei, E. K., & Wettig, S. D. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11040179 · Cited by 58 · see citing works
Insights from pharmacokinetic models of host-microbiome drug metabolism
Zimmermann‐Kogadeeva, M., Zimmermann, M., & Goodman, A. L. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1667724 · Cited by 55 · see citing works
Eigenmann, M. J., Karlsen, T. V., Krippendorff, B., Tenstad, O., Fronton, L., Otteneder, M. B., & Wiig, H. (2017) · The Journal of Physiology · doi:10.1113/jp274819 · Cited by 56 · see citing works
Malik, P. R. V., & Edginton, A. N. (2019) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12456 · Cited by 50 · see citing works
Time-Activity data fitting in molecular Radiotherapy: Methodology and pitfalls
Ivashchenko, O., O’Doherty, J., Hardiansyah, D., Cremonesi, M., Tran‐Gia, J., Hippeläinen, E. T., Stokke, C., Grassi, E., Sandström, M., & Glatting, G. (2023) · Physica Medica · doi:10.1016/j.ejmp.2023.103192 · Cited by 43 · see citing works
Physiologically Based Pharmacokinetic Modeling of Therapeutic Proteins
Wong, H., & Chow, T. W. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.03.038 · Cited by 42 · see citing works
Self-citationTissue Distribution of a Therapeutic Monoclonal Antibody Determined by Large Pore Microdialysis
Jadhav, S. B., Khaowroongrueng, V., Fueth, M., Otteneder, M. B., Richter, W., & Derendorf, H. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.03.033 · Cited by 41 · see citing works
Proteolysis and Oxidation of Therapeutic Proteins After Intradermal or Subcutaneous Administration
Varkhede, N. R., Bommana, R., Schöneich, C., & Forrest, M. L. (2019) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2019.08.005 · Cited by 40 · see citing works
Gilardi, D., Gabbiadini, R., Allocca, M., Correale, C., Fiorino, G., Furfaro, F., Zilli, A., Peyrin‐Biroulet, L., & Danese, S. (2020) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2020.1785868 · Cited by 39 · see citing works
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
Fairman, K., Li, M., Ning, B., & Lumen, A. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114468 · Cited by 29 · see citing works
Vizirianakis, I. S., Miliotou, Α. N., Mystridis, G. A., Andriotis, E. G., Andreadis, I. I., Papadopoulou, L. C., & Fatouros, D. G. (2019) · Expert Review of Precision Medicine and Drug Development · doi:10.1080/23808993.2019.1605828 · Cited by 25 · see citing works
Exploring the fate of inhaled monoclonal antibody in the lung parenchyma by microdialysis
Guillon, A., Pardessus, J., Lhommet, P., Parent, C., Respaud, R., Marchand, D., Montharu, J., Monte, M. D., Janiak, P., Boixel, C., et al. (2019) · mAbs · doi:10.1080/19420862.2018.1556081 · Cited by 25 · see citing works
Xiao, J. J., Chen, J. S., Lum, B. L., & Graham, R. (2017) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000513 · Cited by 24 · see citing works
Talkington, A., Cao, Y., Kearsley, A. J., & Lai, S. K. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115716 · Cited by 22 · see citing works
Malla, R. R., Marni, R., & Chakraborty, A. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188898 · Cited by 22 · see citing works
Sego, T. J., Aponte-Serrano, J. O., Gianlupi, J. F., Heaps, S. R., Breithaupt, K., Brusch, L., Crawshaw, J. R., Osborne, J. M., Quardokus, E. M., Plemper, R. K., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.27.064139 · Cited by 15 · see citing works
van de Meeberg, M. M., Seinen, M. L., Fidder, H. H., Lin, M., Oldenburg, B., de Boer, N. K. H., Bouma, G., de Jonge, R., Bulatović-Ćalasan, M., & (ICC), T. D. I. O. C. A. C. (2022) · BMC Gastroenterology · doi:10.1186/s12876-022-02439-y · Cited by 13 · see citing works
Cai, X., Wu, W., Guo, G., Chen, J., Xu, J., Lin, W., Huang, P., Lin, C., & Lin, R. (2024) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2024.106807 · Cited by 10 · see citing works
Pharmacokinetics and Pharmacodynamics of T-Cell Bispecifics in the Tumour Interstitial Fluid
Eigenmann, M. J., Karlsen, T. V., Wagner, M., Tenstad, O., Weinzierl, T., Fauti, T., Grimm, H. P., Skogstrand, T., Klein, C., Sam, J., et al. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122105 · Cited by 10 · see citing works
Liu, S., & Shah, D. K. (2022) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000460 · Cited by 10 · see citing works
Rose, R. H., Sepp, A., Stader, F., Gill, K. L., Liu, C., & Gardner, I. B. (2022) · Xenobiotica · doi:10.1080/00498254.2022.2133649 · Cited by 7 · see citing works
Drug Disposition Considerations in Pharmaceutical Product
Maheshwari, R., Sharma, P. A., Seth, A., Taneja, N., Tekade, M., & Tekade, R. K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814423-7.00010-1 · Cited by 5 · see citing works
Lee, E., Chary, A., Gerelkhuu, Z., Weber, P., Virmani, I., Brugger, B. A., Ribeiro, I. R. S., Brun, E., Lacconi, V., Bang, H., et al. (2026) · Nano Convergence · doi:10.1186/s40580-026-00566-w · Cited by 4 · see citing works
The science of pharmacokinetics: an overview and applications
Ghazi, I. M., & Cawley, M. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-820007-0.00011-8 · Cited by 3 · see citing works
IMPORTANCE OF SUFFICIENT TIME POINTS FOR EFFICIENT PHARMACOKINETIC (PK) COMPARTMENTAL MODELING
Nandi, T. (2023) · International Journal of Applied Pharmaceutics · doi:10.22159/ijap.2023v15i1.46553 · Cited by 3 · see citing works
Experimental Planning and Execution
Mullane, K., Curtis, M. J., & Williams, M. J. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804725-5.00002-1 · Cited by 3 · see citing works
Jelliffe, R. W., & Bayard, D. S. (2018) · The AAPS Journal · doi:10.1208/s12248-018-0185-x · Cited by 3 · see citing works
Preclinical Studies to Enable First in Human Clinical Trials
Chopra, R., & Raynaud, F. I. (2020) · Springer eBooks · doi:10.1007/978-3-030-47682-3_3 · Cited by 3 · see citing works
Khera, E., Kim, J., Stein, A. M., Ratanapanichkich, M., & Thurber, G. M. (2023) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.122.001540 · Cited by 3 · see citing works
Carrara, L., Magni, P., Teutonico, D., Pasotti, L., Pasqua, O. E. D., & Kloprogge, F. (2020) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2020.105359 · Cited by 3 · see citing works
Systems Biology: Methods and Applications
Titz, B., Knorr, A., Sewer, A., Martin, F. P., Ivanov, N. V., Talikka, M., Suarez, I. G., Peitsch, M. C., & Hoeng, J. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12333-9 · Cited by 2 · see citing works
Gao, Y., Zhong, Y., Guan, R., Yu, Q., Liu, H., Tuersun, A., Zhang, Y., Pang, L., Hu, X., & Ma, G. (2025) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2025.100199 · Cited by 1 · see citing works
Pharmakokinetische Modellierung in der Nuklearmedizin
Kletting, P., & Glatting, G. (2018) · Der Nuklearmediziner · doi:10.1055/s-0043-125347 · Cited by 1 · see citing works
Precision medicine and drug targeting
Petrak, K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813665-2.00004-1 · Cited by 1 · see citing works
Role of Clinical Pharmacokinetics Studies in Contemporary Oncology Drug Development
Uckun, F. M., & Qazi, S. (2020) · Springer eBooks · doi:10.1007/978-3-319-68864-0_24 · Cited by 1 · see citing works
Pharmacokinetic considerations of antibody therapeutics
Wong, H., & Wright, M. R. (2016) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2002
Self-citationRole of Clinical Pharmacokinetics Studies in Contemporary Oncology Drug Development
Uckun, F. M., & Qazi, S. (2018) · Springer eBooks · doi:10.1007/978-3-319-56637-5_24-1
Pharmacovigilance of Antivenoms in Toxicological Emergencies
Esquivel, A., Mendoza, G., Soria, R., & Velázquez, N. (2019) · Latin American Journal of Clinical Sciences and Medical Technology · doi:10.34141/ljcs3729722
Physiologically Based Pharmacokinetic Modeling of Monoclonal Antibodies in Children
Malik, P. R. V. (2021) · UWSpace (University of Waterloo)
van de Meeberg, M. M., Seinen, M. L., Fidder, H. H., Lin, M., Oldenburg, B., de Boer, N. K. H., Bouma, G., de Jonge, R., & Bulatović Ćalasan, M. (2022) · Figshare · doi:10.6084/m9.figshare.20408662
van de Meeberg, M. M., Seinen, M. L., Fidder, H. H., Lin, M., Oldenburg, B., de Boer, N. K. H., Bouma, G., de Jonge, R., & Bulatović Ćalasan, M. (2022) · Figshare · doi:10.6084/m9.figshare.20408656
van de Meeberg, M. M., Seinen, M. L., Fidder, H. H., Lin, M., Oldenburg, B., de Boer, N. K. H., Bouma, G., de Jonge, R., & Bulatović Ćalasan, M. (2022) · Figshare · doi:10.6084/m9.figshare.20408659
Small-Molecule Drug Discovery: Evolution of Medicinal Chemistry and Holistic Approaches
Alzeer, J. (2026) · Springer eBooks · doi:10.1007/978-981-95-6378-4_6
CURE: a phase-based therapeutic framework for chronic inflammation
Kurzen, N., Weißinger, S., & Kurzen, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1826568
Surowka, M., Kober, T., Matscheko, D., Ehler, A., Macedo, W., Assisi, D., Challier, J., Sobieniecki, A., Gianotti, R., Bransi, A., et al. (2026) · Antibody Therapeutics · doi:10.1093/abt/tbag038
- Authors
- Ferl, G. Z., Theil, F., & Wong, H.
- Affiliations
- Genentech (US)
- UCB Pharma (Belgium) (BE)
- University of British Columbia (CA)
- Corresponding author
- Ferl, Gregory Z.
- Venue
- Biopharmaceutics & Drug Disposition
- Publisher
- Wiley
- Published
- 2016-03
- Volume
- 37
- Issue
- 2
- Pages
- 75-92
- ISSN
- 0142-2782 (ISSN-L)
- 1099-081X
- OpenAlex
- W1930401516
- Cited by
- 54
- References
- 80
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 2
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biopharmaceutics & Drug Disposition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- physiologically based pharmacokinetic modeling, therapeutic antibodies, small molecule drugs, drug absorption, drug distribution, drug metabolism, drug elimination, lymphatic system, target-mediated drug disposition, tissue catabolism, oral versus subcutaneous administration
- MeSH terms
- Animals, Antibodies, Monoclonal, Humans, Models, Biological
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
