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Research ArticleSymposium Report

Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting

Edward T. Morgan, Joseph L. Dempsey, Sylvie M. Mimche, Tracey J. Lamb, Supriya Kulkarni, Julia Yue Cui, Hyunyoung Jeong and Angela L. Slitt
Drug Metabolism and Disposition May 2018, 46 (5) 503-513; DOI: https://doi.org/10.1124/dmd.117.079905
Edward T. Morgan
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Joseph L. Dempsey
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Sylvie M. Mimche
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Tracey J. Lamb
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Supriya Kulkarni
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Julia Yue Cui
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Hyunyoung Jeong
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Angela L. Slitt
Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia (E.T.M., S.M.M.); Department of Pathology, University of Utah, Salt Lake City, Utah (T.J.L.); Department of Pharmacy Practice and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois (H.J., J.L.D.); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (J.L.D., J.Y.C.); and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S., S.K.)
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Abstract

This article is a report on a symposium entitled “Physiological Regulation of Drug Metabolism and Transport” sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2017 meeting in Chicago, IL. The contributions of physiologic and pathophysiological regulation of drug-metabolizing enzymes and transporters to interindividual variability in drug metabolism are increasingly recognized but in many cases are not well understood. The presentations herein discuss the phenomenology, consequences, and mechanism of such regulation. CYP2D6 transgenic mice were used to provide insights into the mechanism of regulation of this enzyme in pregnancy, via hepatocyte nuclear factor 4α, small heterodimer partner, and retinoids. Regulation of intestinal and hepatic drug-processing enzymes by the intestinal microbiota via tryptophan and its metabolites was investigated. The potential impact of parasitic infections on human drug metabolism and clearance was assessed in mice infected with Schistosoma mansoni or Plasmodium chabaudi chabaudi AS, both of which produced widespread and profound effects on murine hepatic drug-metabolizing enzymes. Finally, the induction of Abcc drug efflux transporters by fasting was investigated. This was demonstrated to occur via a cAMP, protein kinase A/nuclear factor-E2-related factor 2/Sirtuin 1 pathway via antioxidant response elements on the Abcc genes.

Footnotes

    • Received December 7, 2017.
    • Accepted February 22, 2018.
  • This work was supported in part by grants from the National Institutes of Health National Institute of General Medical Sciences [Grants R01GM112746, R01GM111381]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant R01HD089455]; and National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01DK072372].

  • https://doi.org/10.1124/dmd.117.079905.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 46 (5)
Drug Metabolism and Disposition
Vol. 46, Issue 5
1 May 2018
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Research ArticleSymposium Report

Physiological Regulation of Drug Transport and Metabolism

Edward T. Morgan, Joseph L. Dempsey, Sylvie M. Mimche, Tracey J. Lamb, Supriya Kulkarni, Julia Yue Cui, Hyunyoung Jeong and Angela L. Slitt
Drug Metabolism and Disposition May 1, 2018, 46 (5) 503-513; DOI: https://doi.org/10.1124/dmd.117.079905

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Research ArticleSymposium Report

Physiological Regulation of Drug Transport and Metabolism

Edward T. Morgan, Joseph L. Dempsey, Sylvie M. Mimche, Tracey J. Lamb, Supriya Kulkarni, Julia Yue Cui, Hyunyoung Jeong and Angela L. Slitt
Drug Metabolism and Disposition May 1, 2018, 46 (5) 503-513; DOI: https://doi.org/10.1124/dmd.117.079905
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