Membrane transporters in drug development.
Kathleen M. Giacomini,Shiew-Mei Huang,Donald J. Tweedie,Leslie Z. Benet,Kim L. R. Brouwer,Xiaoyan Chu,Amber Dahlin,Raymond Evers,Volker Fischer,Kathleen M. Hillgren,Keith Hoffmaster,Toshihisa Ishikawa,Dietrich Keppler,Richard B. Kim,Caroline A. Lee,Mikko Niemi,Joseph W. Polli,Yuicchi Sugiyama,Peter W. Swaan,Joseph A. Ware,Stephen H. Wright,Sook Wah Yee,Maciej J. Zamek-Gliszczynski,Lei Zhang +23 more
TLDR
Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions, as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.Abstract:
Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.read more
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Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow
Hyun Jung Kim,Dongeun Huh,Geraldine A. Hamilton,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +5 more
TL;DR: This gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.
Patricio Godoy,Nicola J. Hewitt,Ute Albrecht,Melvin E. Andersen,Nariman Ansari,Sudin Bhattacharya,Johannes G. Bode,Jennifer Bolleyn,Christoph Borner,J Böttger,Albert Braeuning,Robert A. Budinsky,Britta Burkhardt,Neil R. Cameron,Giovanni Camussi,Chong Su Cho,Yun Jaie Choi,J. Craig Rowlands,Uta Dahmen,Georg Damm,Olaf Dirsch,María Teresa Donato,Jian Dong,Steven Dooley,Dirk Drasdo,Dirk Drasdo,Dirk Drasdo,Rowena Eakins,Karine Sá Ferreira,Valentina Fonsato,Joanna Fraczek,Rolf Gebhardt,Andrew Gibson,Matthias Glanemann,Christopher E. Goldring,María José Gómez-Lechón,Geny M. M. Groothuis,Lena Gustavsson,Christelle Guyot,David Hallifax,Seddik Hammad,Adam S. Hayward,Dieter Häussinger,Claus Hellerbrand,Philip Hewitt,Stefan Hoehme,Hermann-Georg Holzhütter,J. Brian Houston,Jens Hrach,Kiyomi Ito,Hartmut Jaeschke,Verena Keitel,Jens M. Kelm,B. Kevin Park,Claus Kordes,Gerd A. Kullak-Ublick,Edward L. LeCluyse,Peng Lu,Jennifer Luebke-Wheeler,Anna Lutz,Daniel J. Maltman,Madlen Matz-Soja,Patrick D. McMullen,Irmgard Merfort,Simon Messner,Christoph Meyer,Jessica Mwinyi,Dean J. Naisbitt,Andreas K. Nussler,Peter Olinga,Francesco Pampaloni,Jingbo Pi,Linda J. Pluta,Stefan Przyborski,Anup Ramachandran,Vera Rogiers,Cliff Rowe,Celine Schelcher,Kathrin Schmich,Michael Schwarz,Bijay Singh,Ernst H. K. Stelzer,Bruno Stieger,Regina Stöber,Yuichi Sugiyama,Ciro Tetta,Wolfgang E. Thasler,Tamara Vanhaecke,Mathieu Vinken,Thomas S. Weiss,Agata Widera,Courtney G. Woods,Jinghai James Xu,Kathy Yarborough,Jan G. Hengstler +94 more
TL;DR: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro and how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes.
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An atlas of genetic influences on human blood metabolites
So-Youn Shin,Eric B. Fauman,Ann-Kristin Petersen,Jan Krumsiek,Rita Santos,Jie Huang,Matthias Arnold,Idil Erte,Vincenzo Forgetta,Tsun-Po Yang,Klaudia Walter,Cristina Menni,Lu Chen,Lu Chen,Louella Vasquez,Ana M. Valdes,Ana M. Valdes,Craig L. Hyde,Vicky Wang,Daniel Ziemek,Phoebe M. Roberts,Li Xi,Elin Grundberg,Melanie Waldenberger,J. Brent Richards,Robert P. Mohney,Michael V. Milburn,Sally John,Jeff K. Trimmer,Fabian J. Theis,John P. Overington,Karsten Suhre,M. Julia Brosnan,Christian Gieger,Gabi Kastenmüller,Tim D. Spector,Nicole Soranzo +36 more
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Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine
Chiranjib Chakraborty,Chiranjib Chakraborty,Ashish Ranjan Sharma,Garima Sharma,C. George Priya Doss,Sang-Soo Lee +5 more
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Physiologically-based pharmacokinetics in drug development and regulatory science.
TL;DR: Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation.
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