Evidence map›Paper›PMID 24829289›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2014

Ontogeny of human hepatic and intestinal transporter gene expression during childhood: age matters.

Miriam G Mooij, Ute I Schwarz, Barbara A E de Koning, J Steven Leeder, Roger Gaedigk, Janneke N Samsom, Edwin Spaans, Johannes B van Goudoever, Dick Tibboel, Richard B Kim and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 3 pooled it
6.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 3 syntheses or guidelines pooled it, 148 citations in OpenAlex.

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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Miriam G MooijIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Ute I SchwarzIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Barbara A E de KoningIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
J Steven LeederIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Roger GaedigkIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Janneke N SamsomIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Edwin SpaansIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Johannes B van GoudoeverIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Dick TibboelIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Richard B KimIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.).
Saskia N de WildtIntensive Care and Department of Pediatric Surgery (M.G.M., S.N.W., B.A.E.K., E.S., D.T.), and Laboratory of Pediatrics, Division of Gastroenterology and Nutrition (J.N.S.), Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada (U.I.S., R.B.K.); Division of Clinical Pharmacology and Therapeutic Innovation, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L., R.G.); Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, and Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands (J.B.G.) s.dewildt@erasmusmc.nl.
Western University · CAAcademic Medical Center · NLErasmus MC - Sophia Children’s Hospital · NLChildren's Mercy Hospital · USEmma Kinderziekenhuis · NL

Funding

LABORATORY OF DEVELOPMENTAL BIOLOGYR24HD000836 · NICHD · UNIVERSITY OF WASHINGTON · PI Ian Amos Glass · 1995 to 2026
$16.9M
NICHD NIH HHS R24 HD000836
6 · The paper itself

Abstract

Many drugs prescribed to children are drug transporter substrates. Drug transporters are membrane-bound proteins that mediate the cellular uptake or efflux of drugs and are important to drug absorption and elimination. Very limited data are available on the effect of age on transporter expression. Our study assessed age-related gene expression of hepatic and intestinal drug transporters. Multidrug resistance protein 2 (MRP2), organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3 expression was determined in postmortem liver samples (fetal n = 6, neonatal n = 19, infant n = 7, child n = 2, adult n = 11) and multidrug resistance 1 (MDR1) expression in 61 pediatric liver samples. Intestinal expression of MDR1, MRP2, and OATP2B1 was determined in surgical small bowel samples (neonates n = 15, infants n = 3, adults n = 14). Using real-time reverse-transcription polymerase chain reaction, we measured fetal and pediatric gene expression relative to 18S rRNA (liver) and villin (intestines), and we compared it with adults using the 2(-∆∆Ct) method. Hepatic expression of MRP2, OATP1B1, and OATP1B3 in all pediatric age groups was significantly lower than in adults. Hepatic MDR1 mRNA expression in fetuses, neonates, and infants was significantly lower than in adults. Neonatal intestinal expressions of MDR1 and MRP2 were comparable to those in adults. Intestinal OATP2B1 expression in neonates was significantly higher than in adults. We provide new data that show organ- and transporter-dependent differences in hepatic and intestinal drug transporter expression in an age-dependent fashion. This suggests that substrate drug absorption mediated by these transporters may be subject to age-related variation in a transporter dependent pattern.

Indexed as

AdolescentAdultATP-Binding Cassette, Sub-Family C ProteinsBiological TransportChildChild, PreschoolFemaleGene ExpressionGene OntologyHumansInfantInfant, NewbornIntestinal MucosaLiverLiver-Specific Organic Anion Transporter 1MaleABCC2 protein, humanATP-Binding Cassette, Sub-Family C ProteinsLiver-Specific Organic Anion Transporter 1Membrane Transport ProteinsMultidrug Resistance-Associated Protein 2Organic Anion TransportersOrganic Anion Transporters, Sodium-IndependentSLCO1B1 protein, humanSLCO1B3 protein, humanSolute Carrier Organic Anion Transporter Family Member 1B3

Identifiers

PMID24829289
PMCPMC4109212
OpenAlexW2135148404

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.