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Drug Metabolism & Disposition

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Research ArticleSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Drug Metabolism and Transport During Pregnancy: How Does Drug Disposition Change during Pregnancy and What Are the Mechanisms that Cause Such Changes?

Nina Isoherranen and Kenneth E. Thummel
Drug Metabolism and Disposition February 2013, 41 (2) 256-262; DOI: https://doi.org/10.1124/dmd.112.050245
Nina Isoherranen
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington
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Kenneth E. Thummel
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington
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Abstract

There is increasing evidence that pregnancy alters the function of drug-metabolizing enzymes and drug transporters in a gestational-stage and tissue-specific manner. In vivo probe studies have shown that the activity of several hepatic cytochrome P450 enzymes, such as CYP2D6 and CYP3A4, is increased during pregnancy, whereas the activity of others, such as CYP1A2, is decreased. The activity of some renal transporters, including organic cation transporter and P-glycoprotein, also appears to be increased during pregnancy. Although much has been learned, significant gaps still exist in our understanding of the spectrum of drug metabolism and transport genes affected, gestational age–dependent changes in the activity of encoded drug metabolizing and transporting processes, and the mechanisms of pregnancy-induced alterations. In this issue of Drug Metabolism and Disposition, a series of articles is presented that address the predictability, mechanisms, and magnitude of changes in drug metabolism and transport processes during pregnancy. The articles highlight state-of-the-art approaches to studying mechanisms of changes in drug disposition during pregnancy, and illustrate the use and integration of data from in vitro models, animal studies, and human clinical studies. The findings presented show the complex inter-relationships between multiple regulators of drug metabolism and transport genes, such as estrogens, progesterone, and growth hormone, and their effects on enzyme and transporter expression in different tissues. The studies provide the impetus for a mechanism- and evidence-based approach to optimally managing drug therapies during pregnancy and improving treatment outcomes.

Footnotes

  • This study was supported in part by the National Institutes of Health [Grant U10 HD047892].

  • dx.doi.org/10.1124/dmd.112.050245.

  • Received November 19, 2012.
  • Accepted December 6, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (2)
Drug Metabolism and Disposition
Vol. 41, Issue 2
1 Feb 2013
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Research ArticleSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Pregnancy-Mediated Changes in Drug Disposition

Nina Isoherranen and Kenneth E. Thummel
Drug Metabolism and Disposition February 1, 2013, 41 (2) 256-262; DOI: https://doi.org/10.1124/dmd.112.050245

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Research ArticleSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Pregnancy-Mediated Changes in Drug Disposition

Nina Isoherranen and Kenneth E. Thummel
Drug Metabolism and Disposition February 1, 2013, 41 (2) 256-262; DOI: https://doi.org/10.1124/dmd.112.050245
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  • Article
    • Abstract
    • Introduction
    • Knowledge on Enzyme-Specific Changes during Pregnancy
    • Use of Animal Models to Study Changes in Drug Disposition during Pregnancy
    • Mechanistic Studies Using In Vitro Systems to Evaluate Regulation of Drug-Metabolizing Enzymes and Transporters during Pregnancy
    • Conclusions
    • Acknowledgments
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More in this TOC Section

  • Renal Transporters in Pregnant Mice
  • Gestational Changes in Metabolic Enzyme and Transport Genes
  • Estradiol Induces CYP2B6
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