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

Miriam G Mooij1, Ute I Schwarz1, Barbara A E de Koning1

  • 1Intensive 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.).

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|May 16, 2014
PubMed

Insights

Pediatric drug transporter expression, including multidrug resistance protein 2 (MRP2) and organic anion transporting polypeptides (OATPs), is lower in the liver but varies in the intestines compared to adults, impacting drug absorption.

Area of Science:

  • Pharmacology
  • Genetics
  • Pediatrics

Background:

  • Drug transporters are crucial for drug absorption and elimination.
  • Limited data exist on how age affects drug transporter expression in children.
  • Many pediatric drugs are substrates for these transporters.

Purpose of the Study:

  • To investigate age-related gene expression of key hepatic and intestinal drug transporters.
  • To compare transporter expression in pediatric populations (fetal to child) with adults.

Main Methods:

  • Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to quantify gene expression.
  • Liver and intestinal tissue samples from various pediatric age groups and adults were analyzed.
  • Expression levels were normalized and compared between age groups.

Main Results:

  • Hepatic expression of MRP2, OATP1B1, and OATP1B3 was significantly lower in all pediatric groups compared to adults.
  • Hepatic MDR1 mRNA expression was also lower in fetal, neonatal, and infant groups.
  • Intestinal OATP2B1 expression was higher in neonates than adults, while MDR1 and MRP2 were comparable.

Conclusions:

  • Significant age-dependent differences in hepatic and intestinal drug transporter expression exist.
  • These variations suggest potential age-related changes in the absorption of substrate drugs.
  • Findings highlight the need for age-specific considerations in pediatric drug therapy.

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