From target selection to the minimum acceptable biological effect level for human study: Use of mechanism-based PK/PD modeling to design safe and efficacious biologics

AAPS Journal

Volumn 13, Issue 2, 2011, Pages 169-178

  Yu, Jing ^a   Karcher, Helene ^b   Feire, Adam L ^a   Lowe, Philip J ^b  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

biologics; candidate selection; first in human dosage selection; mechanism based; pharmacokinetic pharmacodynamic model

Indexed keywords

MONOCLONAL ANTIBODY;

ARTICLE; CYTOMEGALOVIRUS; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG TARGETING; HAPLORHINI; MATHEMATICAL MODEL; NONHUMAN; PHARMACODYNAMICS; PREDICTION; STATISTICAL MODEL;

ANIMALS; ANTIBODIES, MONOCLONAL; CYTOMEGALOVIRUS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DELIVERY SYSTEMS; DRUG DESIGN; FEASIBILITY STUDIES; GLYCOPROTEINS; HUMANS; IMMUNOLOGIC FACTORS; MACACA FASCICULARIS; MODELS, BIOLOGICAL; SPECIES SPECIFICITY; TRANSLATIONAL RESEARCH;

EID: 79957466958     PISSN: 15507416     EISSN: None     Source Type: Journal    
DOI: 10.1208/s12248-011-9256-y     Document Type: Article

References (34)

1. TT Hansel H Kropshofer T Singer JA Mitchell AJT George 2010 The safety and side effects of monoclonal antibodies Nat Rev Drug Discovery 9 325 338 10.1038/nrd3003 1:CAS:528:DC%2BC3cXjs1ehurw%3D
2. ED Lobo RJ Hansen JP Balthasar 2004 Antibody pharmacokinetics and pharmacodynamics J Pharm Sci 93 2645 2668 15389672 10.1002/jps.20178 1:CAS:528:DC%2BD2cXpvV2isLk%3D (Pubitemid 39506617)
3. P Kletting D Bunjes SN Reske G Glatting 2009 Improving anti-CD45 antibody radioimmunotherapy using a physiologically based pharmacokinetic model J Nucl Med 50 296 302 19164217 10.2967/jnumed.108.054189
4. GML Meno-Tetang PJ Lowe 2005 On the prediction of the human response: a recycled mechanistic PK/PD approach Basic Clin Pharmacol Tox 96 182 192 10.1111/j.1742-7843.2005.pto960307.x 1:CAS:528:DC%2BD2MXisFSmu7s%3D (Pubitemid 40387994)
5. BM Agoram SW Martin PH van der Graaf 2007 The role of mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modelling in translational research of biologics Drug Discov Today 12 1018 1024 18061880 10.1016/j.drudis.2007.10.002 1:CAS:528:DC%2BD2sXhsVSmurnO (Pubitemid 350180561)
6. N Hayashi Y Tsukamoto WM Sallas PJ Lowe 2007 A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab Brit J Clin Pharmacol 63 548 561 10.1111/j.1365-2125.2006.02803.x 1:CAS:528:DC%2BD2sXntFOrs7w%3D (Pubitemid 46632569)
7. SR Urva VC Yang JP Balthasar 2010 Physiologically based pharmacokinetic model for T84.66: a monoclonal anti-CEA antibody J Pharm Sci 99 1582 1600 19774657 1:CAS:528:DC%2BC3cXmvVGitw%3D%3D
8. HJ Lachmann PJ Lowe SD Felix C Rordorf K Leslie S Madhoo, et al. 2009 In vivo regulation of interleukin 1β in patients with cryopyrin-associated periodic syndromes J Exp Med 206 1029 1036 19364880 10.1084/jem.20082481 1:CAS:528:DC%2BD1MXlvVGmur8%3D
9. P Thygesen P Macheras A Van Peer 2009 Physiologically-based PK/PD modelling of therapeutic macromolecules Pharm Res 26 2543 2550 19847627 10.1007/s11095-009-9990-3 1:CAS:528:DC%2BD1MXhtlCrtbzE
10. Duff, G (Chair). Expert Scientific Group on Phase I Clinical Trials. Final Report. 30th November 2006. The Stationary Office, Norwich, UK. ISBN 10 0 11 703722 2. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH-063117?IdcService=GET-FILE&dID= 136063&Rendition=Web.
11. G Nigro SP Adler R La Torre AM Best 2005 Passive immunization during pregnancy for congenital cytomegalovirus infection N Engl J Med 353 1350 16192480 10.1056/NEJMoa043337 1:CAS:528:DC%2BD2MXhtVGmtL3K (Pubitemid 41362703)
12. S Varnum DN Streblow ME Monroe P Smith KJ Auberry L Pasa-Tolic, et al. 2004 Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome J Virol 78 20 10960 10966 15452216 10.1128/JVI.78.20.10960-10966. 2004 1:CAS:528:DC%2BD2cXotlKjurY%3D (Pubitemid 39299636)
13. AL Fiere RM Roy K Manley T Compton 2010 The glycoprotein B disintegrin-like domain binds to beta 1 integrin to mediate cytomegalovirus entry J Virol 84 19 10026 10374 10.1128/JVI.00710-10
14. AS Perelson AU Neumann M Markowitz JM Leonard DD Ho 1996 HIV-1 dynamics in-vivo-virion clearance rate, infected cell life-span and viral generation time Science 271 1582 1586 8599114 10.1126/science.271.5255.1582 1:CAS:528:DyaK28XhslSjsbY%3D (Pubitemid 26097216)
15. AU Neumann NP Lam H Dahari DR Gretch TE Wiley TJ Layden, et al. 1998 Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy Science 282 103 107 9756471 10.1126/science.282.5386. 103 1:CAS:528:DyaK1cXmsFOjsLc%3D (Pubitemid 28471138)
16. V Ghetie ES Ward 1997 FcRn: the MHC class I-related receptor that is more than an IgG transporter Immunol Today 18 12 592 598 9425738 10.1016/S0167-5699(97)01172-9 1:CAS:528:DyaK1cXptFY%3D (Pubitemid 28012280)
17. A Garg JP Balthasar 2007 Physiologically-based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wild-type and FcRn-knockout mice J Pharmacokinet Pharmocodyn 34 687 709 10.1007/s10928-007-9065-1 1:CAS:528:DC%2BD2sXhtVOitr%2FO (Pubitemid 47477039)
18. RW Clarke N Monnier H Li D Zhou H Browne 2007 Klenerman. Two-color fluorescence analysis of individual virions determines the distribution of the copy number of proteins in herpes simplex particles Biophys J 93 1329 1337 17513380 10.1529/biophysj.107.106351 1:CAS:528:DC%2BD2sXosFCju7w%3D (Pubitemid 47330912)
19. KL Sampaio Y Cavignac YD Steirhof C Sinzger 2005 Human cytomegalovirus labeled with green fluorescent protein for live analysis of intracellular particle movements J Virol 75 2754 2767 10.1128/JVI.79.5.2754-2767.2005 (Pubitemid 40270553)
20. VC Emery, et al. 2002 Human cytomegalovirus (HCMV) replication dynamics in HCMV-naïve- and -experienced immunocompromised hosts J Infect Dis 185 12 1723 1728 12085317 10.1086/340653 (Pubitemid 34615465)
21. G West JH Brown BJ Enquist 1997 A General Model for the Origin of Allometric Scaling Laws in Biology Science 276 5309 122 126 9082983 10.1126/science.276.5309.122 1:CAS:528:DyaK2sXitl2jtro%3D (Pubitemid 27161259)
22. GB West JH Brown BJ Enquist 1999 The fourth dimension of life: fractal geometry and allometric scaling of organisms Science 284 5420 1677 1679 10356399 10.1126/science.284.5420.1677 1:CAS:528:DyaK1MXjs1Kitbo%3D (Pubitemid 29291379)
23. JF Gillooly JH Brown GB West VM Savage EL Charnov 2001 Effects of size and temperature on metabolic rate Science 293 5538 2248 2251 11567137 10.1126/science.1061967 1:CAS:528:DC%2BD3MXntFCrtrk%3D (Pubitemid 32900233)
24. W Wang T Prueksaritanont 2010 Prediction of human clearance of therapeutic proteins: simple allometric scaling method revisited Biopharm Drug Dispos 31 4 253 263 20437464
25. RJ De Boer H Mohri DD Ho AS Perelson 2003 Turnover rates of B cells, T cells, and NK cells in Simian immunodeficiency virus-infected and uninfected Rhesus Macaques J Immunol 170 2479 2487 12594273 (Pubitemid 36245637)
26. DC Macallan DL Wallace Y Zhang H Ghattas B Asquith C De Lara, et al. 2005 B-cell kinetics in humans: rapid turnover of peripheral blood memory cells Blood 105 3633 3640 15644412 10.1182/blood-2004-09-3740 1:CAS:528: DC%2BD2MXjvFejt7o%3D (Pubitemid 40628210)
27. MA Nowak S Bonhoeffer AM Hill R Boehme HC Thomas H McDade 1996 Viral dynamics in hepatitis B virus infection Proc Natl Acad Sci USA 93 4398 4402 8633078 10.1073/pnas.93.9.4398 1:CAS:528:DyaK28XivVKqt7g%3D (Pubitemid 26144299)
28. AS Perelson E Herrmann F Micol S Zeuzem 2005 New kinetic models for the hepatitis C virus Hepatology 42 749 754 16175615 10.1002/hep.20882 1:CAS:528:DC%2BD2MXhtFGlsbjP (Pubitemid 41401110)
29. PY Muller M Milton P Lloyd, et al. 2009 The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies Curr Opin Biotechnol 20 6 722 729 19896825 10.1016/j.copbio.2009.10.013 1:CAS:528:DC%2BD1MXhsV2ks7zE
30. AF Cohen 2010 Developing drug prototypes: pharmacology replaces safety and tolerability? Nat Rev Drug Discov 9 856 865 20847743 10.1038/nrd3227 1:CAS:528:DC%2BC3cXhtFKrtrjE
31. L Gibiansky E Gibiansky 2009 Target-mediated drug disposition model: approximations, identifiability of model parameters and applications to the population pharmacokinetic-pharmacodynamic modeling of biologics Expert Opin Drug Metabol Toxicol 5 7 803 812 10.1517/17425250902992901 1:CAS:528: DC%2BD1MXnsFamsb4%3D
32. PJ Lowe SJ Tannenbaum K Wu P Lloyd J Sims 2009 On setting the first dose in man: quantitating biotherapeutic drug-target binding through pharmacokinetic and pharmacodynamic models Basic Clin Pharmacol Toxicol 106 195 209 20050847 10.1111/j.1742-7843.2009.00513.x
33. B Agoram 2008 Use of pharmacokinetic/pharmacodynamic modelling for starting dose selction in first-in-human trials of high-risk biologics Br J Clin Pharmacol 67 153 160 19076987 10.1111/j.1365-2125.2008.03297.x
34. WS Putnam J Li J Haggstrom C Ng S Kadkhodayan-Fischer M Cheu, et al. 2008 Use of quantitative pharmacology in the development of HAE1, a high affinity anti-IgE monoclonal antibody AAPS J 10 425 430 18686041 10.1208/s12248-008-9045- 4 1:CAS:528:DC%2BD1cXhtlOgsbnM