Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper

被引：65

作者：

Kraynov, Eugenia ^{[1
]}

Kamath, Amrita V. ^{[2
]}

Walles, Markus ^{[3
]}

Tarcsa, Edit ^{[4
]}

Deslandes, Antoine ^{[5
]}

Iyer, Ramaswamy A. ^{[6
]}

Datta-Mannan, Amita ^{[7
,8
,9
]}

Sriraman, Priya ^{[10
]}

Bairlein, Michaela ^{[11
]}

Yang, Johnny J. ^{[12
]}

Barfield, Matthew ^{[13
]}

Xiao, Guangqing ^{[14
]}

Escandon, Enrique ^{[15
]}

Wang, Weirong ^{[16
]}

Rock, Dan A. ^{[17
]}

Chemuturi, Nagendra V. ^{[18
]}

Moore, David J. ^{[19
]}

机构：

[1] Pfizer Inc, Pharmacokinet Dynam & Metab, La Jolla, CA USA

[2] Genentech Inc, Preclin & Translat Pharmacokinet & Pharmacodynam, San Francisco, CA 94080 USA

[3] Novartis Pharmaceut, Novartis Inst BioMed Res, Drug Metab & Pharmacokinet, Basel, Switzerland

[4] AbbVie, Drug Metab Pharmacokinet & Bioanal Dept, Worcester, MA USA

[5] Sanofi, Disposit Safety & Anim Res, Vitry Sur Seine, France

[6] Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Princeton, NJ USA

[7] Eli Lilly & Co, Dept Drug Disposit, Indianapolis, IN 46285 USA

[8] Eli Lilly & Co, Dept Dev, Indianapolis, IN 46285 USA

[9] Eli Lilly & Co, Dept Commercializat, Indianapolis, IN 46285 USA

[10] Celgene Corp, Drug Metab & Pharmacokinet, Summit, NJ USA

[11] Bayer Pharma AG, Drug Metab & Pharmacokinet, Wuppertal, Germany

[12] Takeda Pharmaceut Int Co, Drug Metab & Pharmacokinet, Boston, MA USA

[13] GlaxoSmithKline R&D, Drug Metab & Pharmacokinet, Bioanalyt Sci & Toxicokinet, Ware, Herts, England

[14] Biogen, Preclin Pharmacokinet & Vitro ADME, Cambridge, MA USA

[15] Merck Res Labs, Biol Discovery Drug Metab & Pharmacokinet & Bioan, Palo Alto, CA USA

[16] Janssen R&D, Biol Clin Pharmacol, Spring House, PA USA

[17] Amgen Pharmacokinet & Drug Metab, Thousand Oaks, CA USA

[18] Seattle Genet Inc, Seattle, WA USA

[19] Roche Innovat Ctr, Dept Pharmaceut Sci, New York, NY USA

来源：

DRUG METABOLISM AND DISPOSITION | 2016年 / 44卷 / 05期

关键词：

TRASTUZUMAB EMTANSINE; BIOANALYSIS; CATABOLISM; PHARMACOKINETICS; STABILITY; ASSAYS; CELLS;

D O I：

10.1124/dmd.115.068049

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014. This white paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs.

引用

页码：617 / 623

页数：7

共 31 条

[1] Antibody-drug conjugates - a perfect synergy
Adair, John R.
Howard, Philip W.
Hartley, John A.
Williams, David G.
Chester, Kerry A.
[J]. EXPERT OPINION ON BIOLOGICAL THERAPY, 2012, 12 (09) : 1191 - 1206
[2] Contribution of linker stability to the activities of anticancer immunoconjugates
Alley, Stephen C.
Benjamin, Dennis R.
Jeffrey, Scott C.
Okeley, Nicole M.
Meyer, Damon L.
Sanderson, Russell J.
Senter, Peter D.
[J]. BIOCONJUGATE CHEMISTRY, 2008, 19 (03) : 759 - 765
[3] Antibody-drug conjugates: targeted drug delivery for cancer
Alley, Stephen C.
Okeley, Nicole M.
Senter, Peter D.
[J]. CURRENT OPINION IN CHEMICAL BIOLOGY, 2010, 14 (04) : 529 - 537
[4] The Pharmacologic Basis for Antibody-Auristatin Conjugate Activity
Alley, Stephen C.
Zhang, Xinqun
Okeley, Nicole M.
Anderson, Martha
Law, Che-Leung
Senter, Peter D.
Benjamin, Dennis R.
[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, 330 (03) : 932 - 938
[5] Impact of Drug Conjugation on Pharmacokinetics and Tissue Distribution of Anti-STEAP1 Antibody-Drug Conjugates in Rats
Boswell, C. Andrew
Mundo, Eduardo E.
Zhang, Crystal
Bumbaca, Daniela
Valle, Nicole R.
Kozak, Katherine R.
Fourie, Aimee
Chuh, Josefa
Koppada, Neelima
Saad, Ola
Gill, Herman
Shen, Ben-Quan
Rubinfeld, Bonnee
Tibbitts, Jay
Kaur, Surinder
Theil, Frank-Peter
Fielder, Paul J.
Khawli, Leslie A.
Lin, Kedan
[J]. BIOCONJUGATE CHEMISTRY, 2011, 22 (10) : 1994 - 2004
[6] Carrasco-Triguero M, 2013, BIOANALYSIS, V5, P1007, DOI [10.4155/bio.13.64, 10.4155/BIO.13.64]
[7] Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies
Deslandes, Antoine
[J]. MABS, 2014, 6 (04) : 859 - 870
[8] ADME of Antibody-Maytansinoid Conjugates
Erickson, Hans K.
Lambert, John M.
[J]. AAPS JOURNAL, 2012, 14 (04): : 799 - 805
[9] The Effect of Different Linkers on Target Cell Catabolism and Pharmacokinetics/Pharmacodynamics of Trastuzumab Maytansinoid Conjugates
Erickson, Hans K.
Phillips, Gail D. Lewis
Leipold, Douglas D.
Provenzano, Carmela A.
Mai, Elaine
Johnson, Holly A.
Gunter, Bert
Audette, Charlene A.
Gupta, Manish
Pinkas, Jan
Tibbitts, Jay
[J]. MOLECULAR CANCER THERAPEUTICS, 2012, 11 (05) : 1133 - 1142
[10] Gorovits B, 2015, BIOANALYSIS, V7, P1559, DOI [10.4155/bio.15.106, 10.4155/BIO.15.106]

← 1 2 3 4 →