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Xenobiotica
the fate of foreign compounds in biological systems
Volume 42, 2012 - Issue 1: Special Issue: Marking the Closure of the Drug Metabolism Department (PDM) at Pfizer’s Sandwich Laboratories
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Review Article

Full efficacy with no CNS side-effects: unachievable panacea or reality? DMPK considerations in design of drugs with limited brain penetration

Susan ColeDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UKCorrespondence[email protected]
,
Sharan BagalWorldwide Medicinal Chenistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
,
Ayman El-KattanDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, USA
,
Katherine FennerDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
,
Tanya HayDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
,
Sarah KempshallDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
,
Graham LunnWorldwide Medicinal Chenistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
,
Manthena VarmaDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, USA
,
Paul StuppleWorldwide Medicinal Chenistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
&
William SpeedDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK
 show all
Pages 11-27 | Received 29 Jun 2011, Accepted 23 Aug 2011, Published online: 04 Oct 2011

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Mirko Rivara & Valentina Zuliani. (2016) Novel sodium channel antagonists in the treatment of neuropathic pain. Expert Opinion on Investigational Drugs 25:2, pages 215-226.
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Bo Feng, Manthena V Varma, Chester Costales, Hui Zhang & Larry Tremaine. (2014) In vitro and in vivo approaches to characterize transporter-mediated disposition in drug discovery. Expert Opinion on Drug Discovery 9:8, pages 873-890.
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Kiril Lanevskij, Pranas Japertas & Remigijus Didziapetris. (2013) Improving the prediction of drug disposition in the brain. Expert Opinion on Drug Metabolism & Toxicology 9:4, pages 473-486.
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Travis T Wager, Jennifer L Liras, Scot Mente & Patrick Trapa. (2012) Strategies to minimize CNS toxicity: in vitro high-throughput assays and computational modeling. Expert Opinion on Drug Metabolism & Toxicology 8:5, pages 531-542.
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Articles from other publishers (23)

Liyue Huang, Mary C. Wells & Zhiyang Zhao. (2020) A Practical Perspective on the Evaluation of Small Molecule CNS Penetration in Drug Discovery. Drug Metabolism Letters 13:2, pages 78-94.
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Christine C. Orozco, Karen Atkinson, Sangwoo Ryu, George Chang, Christopher Keefer, Jian Lin, Keith Riccardi, Robert K. Mongillo, David Tess, Kevin J. Filipski, Amit S. Kalgutkar, John Litchfield, Dennis Scott & Li Di. (2020) Structural attributes influencing unbound tissue distribution. European Journal of Medicinal Chemistry 185, pages 111813.
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Kimberly Holt, Swati Nagar & Ken Korzekwa. (2019) Methods to Predict Volume of Distribution. Current Pharmacology Reports 5:5, pages 391-399.
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Sharan K. Bagal, Kiyoyuki OmotoDavid C. BlakemorePeter J. BungayJames G. BilslandPhilip J. ClarkeMatthew S. Corbett, Ciaran N. Cronin, J. Jean Cui, Rebecca DiasNeil J. FlanaganSamantha E. Greasley, Rachel GrimleyEric Johnson, David FengasLinda KitchingMichelle L. Kraus, Indrawan McAlpine, Asako Nagata, Gareth J. WaldronJoseph S. Warmus. (2018) Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors. Journal of Medicinal Chemistry 62:1, pages 247-265.
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Sharan K. Bagal, Mark AndrewsBruce M. Bechle, Jianwei Bian, James BilslandDavid C. BlakemoreJohn F. Braganza, Peter J. BungayMatthew S. Corbett, Ciaran N. Cronin, Jingrong Jean Cui, Rebecca DiasNeil J. FlanaganSamantha E. Greasley, Rachel GrimleyKim JamesEric Johnson, Linda KitchingMichelle L. Kraus, Indrawan McAlpine, Asako Nagata, Sacha Ninkovic, Kiyoyuki OmotoStephanie Scales, Sarah E. SkerrattJianmin Sun, Michelle Tran-Dubé, Gareth J. WaldronFen Wang & Joseph S. Warmus. (2018) Discovery of Potent, Selective, and Peripherally Restricted Pan-Trk Kinase Inhibitors for the Treatment of Pain. Journal of Medicinal Chemistry 61:15, pages 6779-6800.
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Joana Bicker, Ana Fortuna, Gilberto Alves, Patrício Soares-da-Silva & Amílcar Falcão. (2017) Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol- O -Methyltransferase Inhibitors . Drug Metabolism and Disposition 45:12, pages 1282-1291.
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Sarah E. SkerrattMark AndrewsSharan K. BagalJames BilslandDavid BrownPeter J. BungaySusan ColeKarl R GibsonRussell JonesInaki MoraoAngus NeddermanKiyoyuki OmotoColin RobinsonThomas RyckmansKimberly SkinnerPaul StuppleGareth Waldron. (2016) The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain. Journal of Medicinal Chemistry 59:22, pages 10084-10099.
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Timothy P. Heffron. (2016) Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer. Journal of Medicinal Chemistry 59:22, pages 10030-10066.
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Yaofeng Cheng, Ayman El-Kattan, Yan Zhang, Adrian S. Ray & Yurong Lai. (2016) Involvement of Drug Transporters in Organ Toxicity: The Fundamental Basis of Drug Discovery and Development. Chemical Research in Toxicology 29:4, pages 545-563.
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Patrick E. Trapa, Elena Belova, Jenny L. Liras, Dennis O. Scott & Stefan J. Steyn. (2016) Insights From an Integrated Physiologically Based Pharmacokinetic Model for Brain Penetration. Journal of Pharmaceutical Sciences 105:2, pages 965-971.
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Peter Bungay, Sharan Bagal & Andy Pike. 2015. Blood-Brain Barrier in Drug Discovery. Blood-Brain Barrier in Drug Discovery 446 462 .
Andreas Reichel. 2015. Blood-Brain Barrier in Drug Discovery. Blood-Brain Barrier in Drug Discovery 5 41 .
Edward H. Kerns. 2015. Blood-Brain Barrier in Drug Discovery. Blood-Brain Barrier in Drug Discovery 284 295 .
Stephen M. Lynch, Laykea Tafesse, Kevin Carlin, Parijat Ghatak, Bin Shao, Haissam Abdelhamid & Donald J. Kyle. (2015) N-Aryl azacycles as novel sodium channel blockers. Bioorganic & Medicinal Chemistry Letters 25:1, pages 48-52.
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Sharan Bagal & Peter Bungay. (2014) Restricting CNS penetration of drugs to minimise adverse events: role of drug transporters. Drug Discovery Today: Technologies 12, pages e79-e85.
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Donna A. Volpe, Hong Shen & Praveen V. Balimane. 2014. Predictive ADMET. Predictive ADMET 263 290 .
Richard B. Silverman & Mark W. Holladay. 2014. The Organic Chemistry of Drug Design and Drug Action. The Organic Chemistry of Drug Design and Drug Action 333 356 .
Andreas Reichel. 2014. Drug Delivery to the Brain. Drug Delivery to the Brain 339 374 .
J C Kalvass, J W Polli, D L Bourdet, B Feng, S-M Huang, X Liu, Q R Smith, L K Zhang & M J Zamek-Gliszczynski. (2013) Why Clinical Modulation of Efflux Transport at the Human Blood–Brain Barrier Is Unlikely: The ITC Evidence-Based Position. Clinical Pharmacology & Therapeutics 94:1, pages 80-94.
Crossref
Li Di, Haojing Rong & Bo Feng. (2012) Demystifying Brain Penetration in Central Nervous System Drug Discovery. Journal of Medicinal Chemistry 56:1, pages 2-12.
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Sharan K. Bagal & Peter J. Bungay. (2012) Minimizing Drug Exposure in the CNS while Maintaining Good Oral Absorption. ACS Medicinal Chemistry Letters 3:12, pages 948-950.
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G Moreno-Sanz, O Sasso, A Guijarro, O Oluyemi, R Bertorelli, A Reggiani & D Piomelli. (2012) Pharmacological characterization of the peripheral FAAH inhibitor URB937 in female rodents: interaction with the Abcg2 transporter in the blood-placenta barrier. British Journal of Pharmacology 167:8, pages 1620-1628.
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Graham Lunn, Charles E. Mowbray, Wai L. S. Liu, Valerie M. Joynson, Tanya Hay & Michael Yeadon. (2012) The discovery and profile of PF-0868087, a CNS-sparing histamine H3 receptor antagonist for the treatment of allergic rhinitis. Med. Chem. Commun. 3:3, pages 339-343.
Crossref

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