Plasma Protein Binding of Challenging Compounds J. Pharm. Sci.  2015 Aug; 104(8):2627-36  Keith Riccardi, Shannon Cawley, Philip Yates, Cheng Chang, Carrie Funck, Mark Niosi, Jian Lin, Li Di Pharmacokintics, Dynamics and Metabolism, Pfizer Inc.

Protein-Binding Characteristics of Voriconazole Determined by High-Throughput Equilibrium Dialysis Journal of Pharmaceutical Sciences 103:2565–2570, 2014 Kim Vanstraelen, Joost Wauters, Henriette De Loor, Ine Vercammen, Pieter Annaert, Katrien Lagrou, Isabel Spriet KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, University Hospitals Leuven, Belgium

Understanding and Reducing the Experimental Variability of In Vitro Plasma Protein Binding measurements Journal of Pharmaceutical Sciences 103:3302–3309, 2014 Haiping Wang, Matt Zrada, Ken Anderson, Ravi Katwaru, Paul Harradine, Bernard Choi, Vince Tong, Natasa Pajkovic, Ralph Mazenko, Kathy Cox, lucinda H. Cohen Department of Pharmacodynamics, Pharmacokinetics and Drug Metabolism Merck Research Laboratories (PDF available)

Validation of 96-well equilibrium dialysis with non-radiolabeled drug for definitive measurement of protein binding and application to clinical development of highly-bound drugs. J Pharm Sci. 2011 Jun;100(6):2498-507.Zamek-Gliszczynski MJ, Ruterbories KJ, Ajamie RT, Wickremsinhe ER, Pothuri L, Rao MV, Basavanakatti VN, Pinjari J, Ramanathan VK, Chaudhary AK. Lilly Research Laboratories (PDF available)

An Integrated Bioanalytical Platform for Supporting High-throughput Serum Protein Binding Screening Rapid Communications in Mass Spectrometry Volume 24, Issue 24, pages 3593–3601, December 2010 Jun Zhang, Wilson Z. Shou, Marianne Vath , Kasia Kieltyka, Jennifer Maloney, Larry Elvebak, Jeremy Stewart, John Herbst and Harold N. Weller Applied Biotechnology, Bristol-Myers Squibb, Wallingford, CT 06492, USA

Semi-Automated Protein Binding Methodology Using Equilibrium Dialysis and A Novel Mixed-Matrix Cassette Approach Journal of Pharmaceutical Sciences, Vol. 99, 5070–5078 (2010) Emile G. Plise, Daniel Tran, Laurent Salphati Drug Metabolism and Pharmacokinetics Department, Automation and Assay Technology, Genentech, Inc., South San Francisco

Plasma / Serum Protein Binding Determinations Current Drug Metabolism, 2008, 9, 854-859 Michael J. Banker and Tracey H. Clark Pharmaceutical R&D, Pfizer Global Research & Development, Groton, Connecticut (PDF available)

Relationship Between Exposure and Nonspecific Binding of Thirty-three Central Nervous System Drugs in Mice DMD January 2005 vol. 33 no.1 175-181 Tristan S. Maurer, Demetria B. DeBartolo, David A. Tess and Dennis O. Scott Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Pfizer Global Research and Development, Groton, Connecticut full text available

Influence of Nonspecific Brain and Plasma Binding on CNS Exposure: Implications For Rational Drug Discovery. Biopharm. Drug Dispos. 2002;23:327–338. Kalvass J.C., &Maurer T.S. Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, CT 

Impact of Nonspecific Binding to Microsomes and Phospholipids on the Inhibition of Cytochrome p4502d6: Implications for Relating In Vitro Inhibition Data to In Vivo Drug Interactions Drug Metab Dispos 2003 31: 606-611. Jeannine M. Margolis and R. Scott Obach Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer Global Research and Development, Groton, Connecticut full text available

Development and Validation of a 96-Well Equilibrium Dialysis Apparatus for Measuring Plasma Protein Binding Journal of Pharmaceutical Sciences, vol. 92, no. 5, May 2003 Michael J. Banker, Tracey H. Clark, John A. Williams Pharmaceutical R&D, Pfizer Global Research & Development, Groton, Connecticut (PDF available)

Improving the Accuracy of Unbound Fraction Measurement of Drug-Protein binding by Preconditioning the RED Membrane Inserts.  Bioanalysis (2020) 12(23), 1699-1708 Zhengqi Ye and Quing Chen Vertex Pharmaceuticals, Inc. Boston

Examination of Cefazolin Plasma Levels in Cardiac Surgery under a Revised Dutch Dosing Regimen J Cardiol Clin Res (2021) 9(1): 1164. Vries-Rink et. al. Erasmus University Medical Center Netherlands (PDF available)

A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market  Molecules 2021, 26, 1396. Brandon et. al. University of Dundee

First‑in‑Human Randomized Trial to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the KDM1A Inhibitor Vafidemstat   CNS Drugs (2021) 35:331–344  Rosa María Antonijoan et. al.   Institut de Recercade l’Hospital de la Santa Creu Barcelona, Spain

Pharmacological Prevention of Neonatal Opioid Withdrawal in a Pregnant Guinea Pig Model Frontiers in Pharmacology (2021)  Volume 11  Article 613328   Safa et. al.  Ohio State University

Mechanistic insights on Clearance and Inhibition Discordance Between Liver Microsomes and Hepatocytes When Clearance in Liver Microsomes is Higher Than Hepatocytes   European Journal of Pharmaceutical Sciences 155 (2020) 105541   Christopher Keefer, Li Di et. Al.   Pfizer Research and Development Groton

In Vitro-In Vivo Correlation (IVIVC) for clearance estimation in earlyADME: the importance of unbound fraction assessment in plasma and microsomes   Poster (2020)  Bressac et. al.  Inventiva Daix, France

The Novel In Vitro Method to Calculate Tissue-to-Plasma Partition Coefficient in Humans for Predicting Pharmacokinetic Profiles by Physiologically-Based Pharmacokinetic Model With High Predictability Journal of Pharmaceutical Sciences 109 (2020) 2345-2355. Mayumi et. al. Research Laboratory for Development, Shionogi & Co., Ltd  Japan

Predicted values for human total clearance of a variety of typical compounds with differently humanized-liver mouse plasma data  Drug Metabolism and Pharmacokinetics 35 (2020) 389-396 Nakayama et. al. Central Pharmaceutical Research Institute, Japan Tabacco Inc.

The use of inactivated brain homogenate to determine the in vitro fraction unbound in brain for unstable compounds  Xenobiotica, (2020) 50:10, 1228-1235

Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls: impact on translational drug development  Nature Scientific Reports volume 9, Article number: 5308 (2019) Gustafsson et. al. Uppsala University, Uppsala, Sweden

Establishment of an In Vitro−In Vivo Correlation for Melanin Binding and the Extension of the Ocular Half-Life of Small-Molecule Drugs  Mol. Pharmaceutics 2019, 16, 4890−4901 Mol. Pharmaceutics 2019, 16, 4890−4901 Jakubiak et. al. Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland

Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases J. Med. Chem. 2015, 58, 1358-1371 Georg Jaeschke et. al. Roche Pharmaceutical Research and Early Development   

Validation of a P-Glycoprotein (P-gp) Humanized Mouse Model by Integrating Selective Absolute Quantification of Human MDR1, Mouse Mdr1a and Mdr1b Protein Expressions with In Vivo Functional Analysis for Blood-Brain Barrier Transport   (2015) PLOS ONE | DOI:10.1371/journal.pone.0118638  Muhammad Waqas Sadiq, Yasuo Uchida, Yutaro Hoshi, Masanori Tachikawa, Tetsuya Terasaki, Margareta Hammarlund-Udenaes  Department of Pharmaceutical Biosciences, Uppsala University, Sweden    

FimH Antagonists: Bioisosteres To Improve the in Vitro and in Vivo PK/PD Profile   J. Med. Chem. 2015, 58, 2221−2239   Simon Kleeb,, Lijuan Pang,  Katharina Mayer, Deniz Eris,Anja Sigl, Roland C. Preston, Pascal Zihlmann, Timothy Sharpe, Roman P. Jakob, Daniela Abgottspon, Aline S. Hutter, Meike Scharenberg, Xiaohua Jiang,  Giulio Navarra, Said Rabbani, Martin Smiesko,  Nathalie Lüdin, Jacqueline Bezençon, Oliver Schwardt, Timm Maier, and Beat Ernst  Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Switzerland 

The Potent BACE1 Inhibitor LY2886721 Elicits Robust Central Aβ Pharmacodynamic Responses in Mice, Dogs, and Humans The Journal of Neuroscience, January 21, 2015 • 35(3):1199 –1210 Patrick C. May, Brian A. Willis, Stephen L. Lowe, Robert A. Dean, Scott A. Monk, Patrick J. Cocke, James E. Audia, Leonard N. Boggs, Anthony R. Borders, Richard A. Brier, David O. Calligaro, Theresa A. Day, Larry Ereshefsky, Jon A. Erickson, Hykop Gevorkyan, Celedon R. Gonzales, Douglas E. James, Stanford S. Jhee, Steven F. Komjathy, Linglin Li, Terry D. Lindstrom, Brian M. Mathes, Ferenc Martényi, Scott M. Sheehan, Stephanie L. Stout, David E. Timm, Grant M. Vaught, Brian M. Watson, Leonard L. Winneroski, Zhixiang Yang, and Dustin J. Mergott  Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana full text available

Identification and Characterization of Sebaceous Gland Atrophy-Sparing DGAT1 Inhibitors  (2014)  PLoS ONE 9(2): e88908. doi:10.1371/journal.pone.0088908       Eric S. Muise, Yonghua Zhu, Andreas Verras, Bindhu V. Karanam, Judith Gorski, Drew Weingarth, Hua V. Lin, Joyce Hwa, John R. Thompson, Guanghui Hu, Jian Liu, Shuwen He, Robert J. DeVita, Dong-Ming Shen, Shirly Pinto*   Discovery and Preclinical Sciences, Merck Research Laboratories    

Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor  Biopharmaceutics & Drug Disposition Biopharm. Drug Dispos. (2014) (wileyonlinelibrary.com) DOI: 10.1002/bdd.1889  Aravind Basavapathruni, Edward J. Olhava, Scott R. Daigle, Carly A. Therkelsen, Lei Jin, P. Ann Boriack-Sjodin, Christina J. Allain, Christine R. Klaus, Alejandra Raimondi, Margaret Porter Scott, Angelos Dovletoglou, Victoria M. Richon, Roy M. Pollock, Robert A. Copeland, Mikel P. Moyer, Richard Chesworth, Paul G. Pearson, and Nigel J. Waters  Epizyme Inc., Cambridge, MA, USA 

Utility of cerebrospinal fluid drug concentration as a surrogate for unbound brain concentration in nonhuman primates. Drug Metab Pharmacokinet. 2014;29(5):419-26. Nagaya Y1, Nozaki Y, Kobayashi K, Takenaka O, Nakatani Y, Kusano K, Yoshimura T, Kusuhara H.  Drug Metabolism and Pharmacokinetics Japan, Eisai Product Creation Systems, Eisai Co., Ltd    

In vitro metabolism, disposition, preclinical pharmacokinetics and prediction of human pharmacokinetics of DNDI-VL-2098, a potential oral treatment for Visceral Leishmaniasis  European Journal of Pharmaceutical Sciences 65 (2014) 147–155  Rao Mukkavilli, Jakir Pinjari , Bhavesh Patel, Shankar Sengottuvelan, Subodh Mondal, Ajit Gadekar, Manas Verma, Jignesh Patel, Lavanya Pothuri, Gopu Chandrashekar, Prabhakar Koiram , Tanukrishnan Harisudhan, Ansari Moinuddin, Delphine Launay, Nimish Vachharajani, Vikram Ramanathan, Denis Martin  Advinus Therapeutics Ltd., Bangalore, India

Identification of a novel, non-tetrahydroquinoline variant of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib, with improved aqueous solubility Xenobiotica. 2014 Jul;44(7):591-605. Amit S. Kalgutkar, Kosea S. Frederick*, Heather L. Hatch, Catherine M. Ambler, David A. Perry, Ravi S. Garigipati, George C. Chang, Bruce A. Lefker, Ronald W. Clark, Lee A. Morehouse, Omar Franconey, and Xiao Hu  Pfizer Inc., PDM, Eastern Point Road, Groton, CT    

Development of Functionally Selective, Small Molecule Agonists at Kappa Opioid Receptors J. Biol. Chem. 2013 288: 36703-36716 Lei Zhou, Kimberly M. Lovell, Kevin J. Frankowski, Stephen R. Slauson, Angela M. Phillips, John M. Streicher, Edward Stahl, Cullen L. Schmid, Peter Hodder, Franck Madoux, Michael D. Cameron, Thomas E. Prisinzano, Jeffrey Aubé, Laura M. Bohn Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute  

Preclinical Characterization of GS-9669, a Thumb Site II Inhibitor of the Hepatitis C Virus NS5B Polymerase Antimicrob Agents Chemother. 2013 February; 57(2): 804–810 Martijn Fenaux, Stacey Eng, Stephanie A. Leavitt, Yu-Jen Lee, Eric M. Mabery, Yang Tian, Daniel Byun, Eda Canales, Michael O. Clarke, Edward Doerffler, Scott E. Lazerwith, Willard Lew, Qi Liu, Michael Mertzman, Philip Morganelli, Lianhong Xu, Hong Ye, Jennifer Zhang, Mike Matles, Bernard P. Murray, Judy Mwangi, Jingyu Zhang, Ahmad Hashash, Steve H. Krawczyk, Alison M. Bidgood, Todd C. Appleby, and William J. Watkins Gilead Sciences, Foster City, California, USA   

Effect of Ritonavir on 99mTechnetium–Mebrofenin Disposition in Humans: A Semi-PBPK Modeling and In Vitro Approach to Predict Transporter-Mediated DDIs CPT Pharmacometrics Syst Pharmacol. 2013 January; 2(1): e20.  N D Pfeifer, S L Goss, B Swift, G Ghibellini,1 M Ivanovic, W D Heizer, L M Gangarosa, and K L R Brouwer University of North Carolina at Chapel Hill  

Targeting the PI3K Pathway in the Brain—Efficacy of a PI3K Inhibitor Optimized to Cross the Blood–Brain Barrier  Clin Cancer Res  November 15, 2012   18;  62391. Laurent Salphati, Timothy P. Heffron, Bruno Alicke, Merry Nishimura, Kai Barck, Richard A. Carano, Jonathan Cheong, Kyle A. Edgar, Joan Greve, Samir Kharbanda, Hartmut Koeppen, Shari Lau, Leslie B. Lee, Jodie Pang, Emile G. Plise, Jenny L. Pokorny, Hani Bou Reslan, Jann N. Sarkaria, Jeffrey J. Wallin, Xiaolin Zhang, Stephen E. Gould, Alan G. Olivero, and Heidi S. Phillips Genentech Inc, South San Francisco, California and Mayo Clinic, Rochester NY