Research ArticleDrug Discovery and Translational Medicine
Using Chimeric Mice with Humanized Livers to Predict Human Drug Metabolism and a Drug-Drug Interaction
Toshihiko Nishimura, Yajing Hu, Manhong Wu, Edward Pham, Hiroshi Suemizu, Menashe Elazar, Michael Liu, Ramazan Idilman, Cihan Yurdaydin, Peter Angus, Catherine Stedman, Brian Murphy, Jeffrey Glenn, Masato Nakamura, Tatsuji Nomura, Yuan Chen, Ming Zheng, William L. Fitch and Gary Peltz
Journal of Pharmacology and Experimental Therapeutics February 2013, 344 (2) 388-396; DOI: https://doi.org/10.1124/jpet.112.198697
Toshihiko Nishimura
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Yajing Hu
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Manhong Wu
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Edward Pham
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Hiroshi Suemizu
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Menashe Elazar
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Michael Liu
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Ramazan Idilman
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Cihan Yurdaydin
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Peter Angus
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Catherine Stedman
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Brian Murphy
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Jeffrey Glenn
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Masato Nakamura
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Tatsuji Nomura
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Yuan Chen
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Ming Zheng
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
William L. Fitch
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
Gary Peltz
Department of Anesthesia (T.N., Y.H., M.W., M.Z., W.L.F., G.P.) and Department of Medicine, Stanford University School of Medicine, Stanford, California (E.P., M.L., M.E., J.G.); Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan (H.S., M.N., T.N.); Genentech, Drug Metabolism and Pharmacokinetics, South San Francisco, California (Y.C.); Hepatology Institute, University of Ankara, Turkey (R.I., C.Y.); Liver Transplant Unit, University of Melbourne, Austin Hospital, Heidelberg, Australia (P.A.); Gastroenterology Department, Christchurch Hospital, and University of Otago, Christchurch, New Zealand (C.S.); and Eiger BioPharmaceuticals, Palo Alto, California (B.M.)
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In this issue
Research ArticleDrug Discovery and Translational Medicine
Chimeric Mice and Human Drug Metabolism
Toshihiko Nishimura, Yajing Hu, Manhong Wu, Edward Pham, Hiroshi Suemizu, Menashe Elazar, Michael Liu, Ramazan Idilman, Cihan Yurdaydin, Peter Angus, Catherine Stedman, Brian Murphy, Jeffrey Glenn, Masato Nakamura, Tatsuji Nomura, Yuan Chen, Ming Zheng, William L. Fitch and Gary Peltz
Journal of Pharmacology and Experimental Therapeutics February 1, 2013, 344 (2) 388-396; DOI: https://doi.org/10.1124/jpet.112.198697
Research ArticleDrug Discovery and Translational Medicine
Chimeric Mice and Human Drug Metabolism
Toshihiko Nishimura, Yajing Hu, Manhong Wu, Edward Pham, Hiroshi Suemizu, Menashe Elazar, Michael Liu, Ramazan Idilman, Cihan Yurdaydin, Peter Angus, Catherine Stedman, Brian Murphy, Jeffrey Glenn, Masato Nakamura, Tatsuji Nomura, Yuan Chen, Ming Zheng, William L. Fitch and Gary Peltz
Journal of Pharmacology and Experimental Therapeutics February 1, 2013, 344 (2) 388-396; DOI: https://doi.org/10.1124/jpet.112.198697
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