Ontogeny of Hepatic Drug Transporters as Quantified by LC-MS/MS Proteomics.

Abstract

Protein expression of major hepatic uptake and efflux drug transporters in human pediatric (n = 69) and adult (n = 41) livers was quantified by liquid chromatography / tandem mass spectroscopy (LC-MS/MS). Transporter protein expression of OCT1, OATP1B3, P-gp, and MRP3 was age-dependent. Particularly, significant differences were observed in transporter expression (P < 0.05) between the following age groups: neonates vs. adults (OCT1, OATP1B3, P-gp), neonates or infants vs. adolescents and/or adults (OCT1, OATP1B3, and P-gp), infants vs. children (OATP1B3 and P-gp), and adolescents vs. adults (MRP3). OCT1 showed the largest increase, of almost 5-fold, in protein expression with age. Ontogenic expression of OATP1B1 was confounded by genotype and was revealed only in livers harboring SLCO1B1*1A/*1A. In livers >1 year, tissues harboring SLCO1B1*14/*1A showed 2.5-fold higher (P < 0.05) protein expression than SLCO1B1*15/*1A. Integration of these ontogeny data in physiologically based pharmacokinetic (PBPK) models will be a crucial step in predicting hepatic drug disposition in children.

DOI: 10.1002/cpt.409

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05010020162017
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@article{Prasad2016OntogenyOH, title={Ontogeny of Hepatic Drug Transporters as Quantified by LC-MS/MS Proteomics.}, author={Bhagwat Prasad and Andrea Gaedigk and Marc Vrana and Roger Gaedigk and J. Steven Leeder and Laurent Salphati and Xiao-yan Chu and G Xiao and Ceca Hop and Raymond Evers and Liqiang Gan and Jashvant D. Unadkat}, journal={Clinical pharmacology and therapeutics}, year={2016}, volume={100 4}, pages={362-70} }