Research ArticleMinireview
Drug Concentration Asymmetry in Tissues and Plasma for Small Molecule–Related Therapeutic Modalities
Donglu Zhang, Cornelis E.C.A. Hop, Gabriela Patilea-Vrana, Gautham Gampa, Herana Kamal Seneviratne, Jashvant D. Unadkat, Jane R. Kenny, Karthik Nagapudi, Li Di, Lian Zhou, Mark Zak, Matthew R. Wright, Namandjé N. Bumpus, Richard Zang, Xingrong Liu, Yurong Lai and S. Cyrus Khojasteh
Drug Metabolism and Disposition October 2019, 47 (10) 1122-1135; DOI: https://doi.org/10.1124/dmd.119.086744
Donglu Zhang
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Cornelis E.C.A. Hop
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Gabriela Patilea-Vrana
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Gautham Gampa
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Herana Kamal Seneviratne
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Jashvant D. Unadkat
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Jane R. Kenny
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Karthik Nagapudi
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Li Di
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Lian Zhou
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Mark Zak
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Matthew R. Wright
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Namandjé N. Bumpus
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Richard Zang
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Xingrong Liu
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Yurong Lai
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
S. Cyrus Khojasteh
Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
Article Information
vol. 47 no. 10 1122-1135
PubMed
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History
- Received February 11, 2019
- Accepted June 10, 2019
- Published online September 19, 2019.
Article Versions
- Earlier version (July 2, 2019 - 12:04).
- You are viewing the most recent version of this article.
Copyright & Usage
Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics
Author Information
- Donglu Zhang,
- Cornelis E.C.A. Hop,
- Gabriela Patilea-Vrana,
- Gautham Gampa,
- Herana Kamal Seneviratne,
- Jashvant D. Unadkat,
- Jane R. Kenny,
- Karthik Nagapudi,
- Li Di,
- Lian Zhou,
- Mark Zak,
- Matthew R. Wright,
- Namandjé N. Bumpus,
- Richard Zang,
- Xingrong Liu,
- Yurong Lai, and
- S. Cyrus Khojasteh
- Genentech, South San Francisco, California (D.Z., C.E.C.A.H., J.R.K., K.N., M.Z., M.R.W., R.Z., S.C.K.); Department of Medicine, Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (H.K.S., N.N.B.); Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (G.G.); Department of Pharmaceutics, University of Washington, Seattle, Washington (G.P.-V., J.D.U.); Biogen, Cambridge, Massachusetts (X.L.); Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut (L.D.); Drug Disposition, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana (L.Z.); and Drug Metabolism, Gilead Sciences, Foster City, California (Y.L.)
- Address correspondence to:
Donglu Zhang, Genentech, 1 DNA Way, South San Francisco, CA 94080. E-mail: Zhang.donglu{at}gene.com; or Cyrus Khojasteh, Genentech, 1 DNA Way, South San Francisco, CA 94080. E-mail: pars{at}gene.com
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Research ArticleMinireview
Tissue Drug Concentrations: Beyond the Free Drug Hypothesis
Donglu Zhang, Cornelis E.C.A. Hop, Gabriela Patilea-Vrana, Gautham Gampa, Herana Kamal Seneviratne, Jashvant D. Unadkat, Jane R. Kenny, Karthik Nagapudi, Li Di, Lian Zhou, Mark Zak, Matthew R. Wright, Namandjé N. Bumpus, Richard Zang, Xingrong Liu, Yurong Lai and S. Cyrus Khojasteh
Drug Metabolism and Disposition October 1, 2019, 47 (10) 1122-1135; DOI: https://doi.org/10.1124/dmd.119.086744
Research ArticleMinireview
Tissue Drug Concentrations: Beyond the Free Drug Hypothesis
Donglu Zhang, Cornelis E.C.A. Hop, Gabriela Patilea-Vrana, Gautham Gampa, Herana Kamal Seneviratne, Jashvant D. Unadkat, Jane R. Kenny, Karthik Nagapudi, Li Di, Lian Zhou, Mark Zak, Matthew R. Wright, Namandjé N. Bumpus, Richard Zang, Xingrong Liu, Yurong Lai and S. Cyrus Khojasteh
Drug Metabolism and Disposition October 1, 2019, 47 (10) 1122-1135; DOI: https://doi.org/10.1124/dmd.119.086744
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