Document Detail


Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?
MedLine Citation:
PMID:  23328895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nina Isoherranen; Kenneth E Thummel
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Publication Detail:
Type:  Comment; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  41     ISSN:  1521-009X     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-07-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  256-62     Citation Subset:  IM    
Export Citation:
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / metabolism*
Adrenal Glands / enzymology*
Animals
Aryldialkylphosphatase / metabolism*
Carboxylesterase / metabolism*
Cholestasis / metabolism*
Cotinine / metabolism*
Cytochrome P-450 Enzyme System / biosynthesis,  genetics,  metabolism*
Estradiol / pharmacology*
Estrogen Receptor alpha / agonists*
Estrogens / pharmacology*
Ethinyl Estradiol / pharmacology*
Female
Fetus / drug effects*
Gene Expression Regulation, Developmental / drug effects*
Glucuronosyltransferase / genetics,  metabolism*
Hepatocytes / drug effects*,  metabolism*
Humans
Hydroxyprogesterones / metabolism*
Intestine, Small / enzymology*
Kidney / enzymology*,  metabolism*
Liver / drug effects*,  enzymology*
Lung / enzymology*
Male
Maternal Behavior*
Membrane Transport Proteins / metabolism*
Multidrug Resistance-Associated Proteins / drug effects*
Organic Anion Transporters / metabolism*
Pesticides / metabolism*
Placenta / drug effects*,  enzymology*
Pregnancy
Progesterone / pharmacology*
RNA, Messenger / biosynthesis*
Smoking / adverse effects*
Taurocholic Acid / metabolism*
Grant Support
ID/Acronym/Agency:
U10HD047892/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Estrogens; 0/Hydroxyprogesterones; 0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/Organic Anion Transporters; 0/Pesticides; 0/RNA, Messenger; 0/multidrug resistance-associated protein 3; 423D2T571U/Ethinyl Estradiol; 4G7DS2Q64Y/Progesterone; 4TI98Z838E/Estradiol; 5E090O0G3Z/Taurocholic Acid; 630-56-8/17-alpha-hydroxy-progesterone caproate; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/retinoic acid 4-hydroxylase; EC 2.4.1.-/UGT2B7 protein, human; EC 2.4.1.17/Glucuronosyltransferase; EC 2.4.1.17/UDP-glucuronosyltransferase 2B15, human; EC 2.4.1.17/UGT2B17 protein, human; EC 3.1.1.1/Carboxylesterase; EC 3.1.8.1/Aryldialkylphosphatase; EC 3.1.8.1/PON1 protein, mouse; K5161X06LL/Cotinine
Comments/Corrections
Comment On:
Drug Metab Dispos. 2013 Feb;41(2):263-9   [PMID:  22837389 ]
Drug Metab Dispos. 2013 Feb;41(2):320-5   [PMID:  22896729 ]
Drug Metab Dispos. 2013 Feb;41(2):275-80   [PMID:  23077105 ]
Drug Metab Dispos. 2013 Feb;41(2):296-304   [PMID:  23129211 ]
Drug Metab Dispos. 2013 Feb;41(2):326-31   [PMID:  23223497 ]
Drug Metab Dispos. 2013 Feb;41(2):332-42   [PMID:  23175668 ]
Drug Metab Dispos. 2013 Feb;41(2):305-11   [PMID:  23209192 ]
Drug Metab Dispos. 2013 Feb;41(2):291-5   [PMID:  23223495 ]
Drug Metab Dispos. 2013 Feb;41(2):312-9   [PMID:  23150428 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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