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 which are important to drug absorption and elimination. Very limited data are available on the effect of age on transporter expression. The aim of this study was to assess age-related gene expression of hepatic and intestinal drug transporters. MRP2, 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 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 RT-PCR, fetal and pediatric gene expression was determined relative to 18S rRNA (liver) and villin (intestines), and compared to adults using the 2-ΔΔCt 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.
- ABC transporters
- drug transport
- hepatobiliary transport
- intestinal transport
- MRP
- multi-drug resistance
- organic anion transport
- p-glycoprotein
- transporters
- The American Society for Pharmacology and Experimental Therapeutics