PT - JOURNAL ARTICLE AU - Miriam G. Mooij AU - Barbara A.E. de Koning AU - Dicky J. Lindenbergh-Kortleve AU - Ytje Simons-Oosterhuis AU - Bianca D van Groen AU - Dick Tibboel AU - Janneke N. Samsom AU - Saskia N. de Wildt TI - Human intestinal PEPT1 transporter expression and localization in preterm and term infants AID - 10.1124/dmd.115.068809 DP - 2016 Jan 01 TA - Drug Metabolism and Disposition PG - dmd.115.068809 4099 - http://dmd.aspetjournals.org/content/early/2016/04/14/dmd.115.068809.short 4100 - http://dmd.aspetjournals.org/content/early/2016/04/14/dmd.115.068809.full AB - The intestinal influx oligopeptide transporter PEPT1 (SLC15A1) is best known for nutrient-derived di- and tripeptide transport. Its role in drug absorption is increasingly recognized. To better understand the disposition of PEPT1 substrate drugs in young infants, we studied intestinal PEPT1 mRNA expression and tissue localization across the pediatric age range. PEPT1 mRNA expression was determined using real time RT-PCR in small intestinal tissues collected from surgical procedures (neonates, infants) or biopsies (older children, adolescents). PEPT1 mRNA relative to villin mRNA expression were compared between neonates/infants and older children and adolescents. PEPT1 was visualized in infant tissue using immunohistochemical staining. Other transporters (MDR1, MRP2 and OATP2B1) were also stained to describe the localization in relation to PEPT1. 26 intestinal samples (n=20 neonates/infants, n=2 pediatric, n=4 adolescents) were analyzed. The young infant samples were collected at a median (range) gestational age at birth of 29.2 weeks (24.7 - 40) and postnatal age of 2.4 weeks (0 - 16.6). The PEPT1 mRNA expression of the neonates/infants was only marginally lower (0.8-fold) than the older children (p<0.05). Similar and clear apical PEPT1 and MRP2 staining, apical and lateral MDR1 staining, and intra-epithelial OATP2B1 staining at the basolateral membrane of the enterocyte was detected in 12 infant and 2 adolescent samples. Although small intestinal PEPT1 expression tended to be lower in neonates than in older children, this difference is small and tissue distribution is similar. This finding suggests similar oral absorption of PEPT1 substrates across the pediatric age range.