ReviewDrug metabolism and disposition: the biological fate of chemicals2019
Drug Concentration Asymmetry in Tissues and Plasma for Small Molecule-Related Therapeutic Modalities.
Open access · bronzeAbstract readReview
In one paragraph
Review in Drug metabolism and disposition: the biological fate of chemicals, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
5.3field-weighted citation impact, top 3% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 118 citations in OpenAlex.
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Corrections and comments
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Authors and funding
17 authors at 7 institutions in 1 country.
Donglu ZhangGenentech, 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.) Zhang.donglu@gene.com pars@gene.com.
Cornelis E C A HopGenentech, 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-VranaGenentech, 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 GampaGenentech, 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 SeneviratneGenentech, 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 UnadkatGenentech, 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 KennyGenentech, 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 NagapudiGenentech, 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 DiGenentech, 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 ZhouGenentech, 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 ZakGenentech, 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 WrightGenentech, 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 BumpusGenentech, 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 ZangGenentech, 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 LiuGenentech, 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 LaiGenentech, 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 KhojastehGenentech, 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.) Zhang.donglu@gene.com pars@gene.com.
Johns Hopkins University · USUniversity of Washington · USEli Lilly (United States) · USJohns Hopkins Medicine · USPfizer (United States) · USUniversity of Minnesota · USGilead Sciences (United States) · US
Funding
LC: HIV Prevention Trials Network - Laboratory Support for the SARS-CoV-2 Seroprevalence Study (CoVPN 5002)UM1AI068613 · NIAID · JOHNS HOPKINS UNIVERSITY · PI SUSAN H ESHLEMAN, Mark A Marzinke · 2011 to 2026
$100.2MUnderstanding Fetal Exposure to Cannabinoids Through In Vitro and In Vivo StudiesP01DA032507 · NIDA · UNIVERSITY OF WASHINGTON · PI UNADKAT, JASHVANT D · 2013 to 2023
$12.4MTrans Network ProjectU54CA210180 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SARKARIA, JANN N. · 2016 to 2020
$10.2MTargeting Kif11 to Treat Glioblastoma Invasion and ProliferationR01NS073610 · NINDS · MAYO CLINIC JACKSONVILLE · PI CANOLL, PETER, ELMQUIST, WILLIAM · 2012 to 2021
$4.3MInfluence of Anti-Angiogenic Therapy on Drug Delivery to Brain TumorsR01NS077921 · NINDS · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, SARKARIA, JANN N. · 2012 to 2016
$2.5MDevelopmental Pharmacology of Antiretroviral Metabolism in Mucosal TissuesR01AI128781 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BUMPUS, NAMANDJE N · 2017 to 2020
$1.6MNCI NIH HHS U54 CA210180NIAID NIH HHS R01 AI128781NIAID NIH HHS UM1 AI068613NIDA NIH HHS P01 DA032507NINDS NIH HHS R01 NS073610NINDS NIH HHS R01 NS077921
Abstract
The well accepted "free drug hypothesis" for small-molecule drugs assumes that only the free (unbound) drug concentration at the therapeutic target can elicit a pharmacologic effect. Unbound (free) drug concentrations in plasma are readily measurable and are often used as surrogates for the drug concentrations at the site of pharmacologic action in pharmacokinetic-pharmacodynamic analysis and clinical dose projection in drug discovery. Furthermore, for permeable compounds at pharmacokinetic steady state, the free drug concentration in tissue is likely a close approximation of that in plasma; however, several factors can create and maintain disequilibrium between the free drug concentration in plasma and tissue, leading to free drug concentration asymmetry. These factors include drug uptake and extrusion mechanisms involving the uptake and efflux drug transporters, intracellular biotransformation of prodrugs, membrane receptor-mediated uptake of antibody-drug conjugates, pH gradients, unique distribution properties (covalent binders, nanoparticles), and local drug delivery (e.g., inhalation). The impact of these factors on the free drug concentrations in tissues can be represented by
Indexed as
AnimalsBiotransformationCell MembraneDrug DiscoveryHumansImmunoconjugatesMembrane Transport ProteinsPlasmaProdrugsTissue DistributionImmunoconjugatesMembrane Transport ProteinsProdrugs
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